- Krishna, Smriti, Seto, Sai-Wang, Jose, Roby, Biros, Erik, Moran, Corey, Wang, Yutang, Clancy, Paula, Golledge, Jonathan
- Authors: Krishna, Smriti , Seto, Sai-Wang , Jose, Roby , Biros, Erik , Moran, Corey , Wang, Yutang , Clancy, Paula , Golledge, Jonathan
- Date: 2016
- Type: Text , Journal article
- Relation: Arteriosclerosis, Thrombosis, and Vascular Biology Vol. 35, no. 2 (2016), p. 389-398
- Full Text: false
- Reviewed:
- Description: OBJECTIVE - : Interaction of the activating sequence in thrombospondin-1 (TSP-1) with the conserved sequence (leucine-serine-lysine-leucine [LSKL]) in the latency-associated peptide region of latent transforming growth factor (TGF)-β complex is important in regulating TGF-β1 activity. We aimed to assess the effect of blocking peptide LSKL on the progression of pre-established abdominal aortic aneurysm in angiotensin II-infused apolipoprotein E-deficient (ApoE) mice. APPROACH AND RESULTS - : Abdominal aortic aneurysm was established in 3-month-old male ApoE mice with subcutaneous infusion of angiotensin II for 28 days. After this, mice received LSKL peptide or control SLLK (serine-leucine-leucine-lysine) peptide (4 mg/kg) via daily intraperitoneal injection for an additional 2 weeks. Administration of LSKL peptide promoted larger suprarenal aortic diameter, as determined by ultrasound and morphometric analysis, and stimulated more severe atherosclerosis within the aortic arch. In addition, mice receiving LSKL peptide exhibited elevated circulating proinflammatory cytokine levels and greater inflammatory cells within the suprarenal aorta compared with controls. Mice receiving LSKL peptide showed low plasma TGF-β1 activity and low levels of aortic tissue phosphorylated to total Smad2/3. Aortic gene expression of TGF-β receptor 1 (TGFBRI) and receptor 2 (TGFBRII), but not TGF-β1 and thrombospondin-1, were lower in mice receiving LSKL peptide than controls. LSKL peptide administration was associated with greater aortic elastin fragmentation and lower expression and activity of the TGF-β1-target gene lysyl oxidase like 1 (LOXL1). CONCLUSIONS - : Attenuation of thrombospondin-1-directed activation of TGF-β1 promotes abdominal aortic aneurysm and atherosclerosis progression in the angiotensin II-infused ApoE mouse model. © 2014 American Heart Association, Inc.
Adjustment for body mass index changes inverse associations of HDL-cholesterol with blood pressure and hypertension to positive associations
- Yang, Guang, Qian, Tingting, Sun, Hui, Xu, Qun, Hou, Xujuan, Hu, Wenqi, Zhang, Guang, Drummond, Grant, Sobey, Christopher, Witting, Paul, Denton, Kate, Charchar, Fadi, Golledge, Jonathan, Wang, Yutang
- Authors: Yang, Guang , Qian, Tingting , Sun, Hui , Xu, Qun , Hou, Xujuan , Hu, Wenqi , Zhang, Guang , Drummond, Grant , Sobey, Christopher , Witting, Paul , Denton, Kate , Charchar, Fadi , Golledge, Jonathan , Wang, Yutang
- Date: 2022
- Type: Text , Journal article
- Relation: Journal of Human Hypertension Vol. 36, no. 6 (2022), p. 570-579
- Full Text:
- Reviewed:
- Description: The associations between high-density lipoprotein cholesterol (HDL-C) and blood pressure (BP) or hypertension are inconsistent in previous studies. This study aimed to assess these associations in a large cohort of Chinese adults and across different age groups. This cross-sectional association study included 22,081 Chinese adults. Associations of HDL-C with BP and hypertension were analyzed using linear or logistic regression, with or without adjustment for confounding factors. HDL-C was inversely associated with BP and hypertension. These associations were still apparent after adjustment for age, sex, fasting plasma glucose, and low-density lipoprotein cholesterol. Sub-analyses revealed: (1) in the whole cohort and females alone, HDL-C was inversely associated with BP and hypertension in young and middle-aged but not older participants; (2) in males alone, HDL-C was not associated with systolic BP or hypertension. However, HDL-C was either inversely, or not, or positively associated with BP in young, middle-aged, and older males, respectively. After further adjustment for body mass index (BMI), the negative associations of HDL-C with BP and hypertension in the whole cohort became positive ones, and the positive associations only presented in males. These findings suggest that further adjustment for BMI changes inverse associations of HDL-cholesterol with BP and hypertension to positive associations in a cohort of Chinese adults. © 2021, The Author(s), under exclusive licence to Springer Nature Limited.
- Authors: Yang, Guang , Qian, Tingting , Sun, Hui , Xu, Qun , Hou, Xujuan , Hu, Wenqi , Zhang, Guang , Drummond, Grant , Sobey, Christopher , Witting, Paul , Denton, Kate , Charchar, Fadi , Golledge, Jonathan , Wang, Yutang
- Date: 2022
- Type: Text , Journal article
- Relation: Journal of Human Hypertension Vol. 36, no. 6 (2022), p. 570-579
- Full Text:
- Reviewed:
- Description: The associations between high-density lipoprotein cholesterol (HDL-C) and blood pressure (BP) or hypertension are inconsistent in previous studies. This study aimed to assess these associations in a large cohort of Chinese adults and across different age groups. This cross-sectional association study included 22,081 Chinese adults. Associations of HDL-C with BP and hypertension were analyzed using linear or logistic regression, with or without adjustment for confounding factors. HDL-C was inversely associated with BP and hypertension. These associations were still apparent after adjustment for age, sex, fasting plasma glucose, and low-density lipoprotein cholesterol. Sub-analyses revealed: (1) in the whole cohort and females alone, HDL-C was inversely associated with BP and hypertension in young and middle-aged but not older participants; (2) in males alone, HDL-C was not associated with systolic BP or hypertension. However, HDL-C was either inversely, or not, or positively associated with BP in young, middle-aged, and older males, respectively. After further adjustment for body mass index (BMI), the negative associations of HDL-C with BP and hypertension in the whole cohort became positive ones, and the positive associations only presented in males. These findings suggest that further adjustment for BMI changes inverse associations of HDL-cholesterol with BP and hypertension to positive associations in a cohort of Chinese adults. © 2021, The Author(s), under exclusive licence to Springer Nature Limited.
An improved 3-(4,5-dmethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl )-2H-tetrazolium proliferation assay to overcome the interference of hydralazine
- Wang, Yutang, Nguyen, Dinh, Yang, Guang, Anesi, Jack, Chai, Zhonglin, Charchar, Fadi, Golledge, Jonathan
- Authors: Wang, Yutang , Nguyen, Dinh , Yang, Guang , Anesi, Jack , Chai, Zhonglin , Charchar, Fadi , Golledge, Jonathan
- Date: 2020
- Type: Text , Journal article
- Relation: Assay and Drug Development Technologies Vol. 18, no. 8 (Dec 2020), p. 379-384
- Relation: https://purl.org/au-research/grants/nhmrc/1062671
- Full Text:
- Reviewed:
- Description: The MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium] assay is one of the most commonly used assays to assess cell proliferation and cytotoxicity, but is subject to interference by testing compounds. Hydralazine, an antihypertensive drug, is commonly investigated in multiple fields such as heart failure, cancer, and blood pressure research. This study reported interference of the MTS assay by hydralazine and a simple modification overcoming this interference. Vascular smooth muscle cells were cultured in the presence or absence of hydralazine (0, 10, 50,100, and 500 mu M) for 2 or 24 h. Cell numbers were analyzed using MTS, trypan blue exclusion, or microscopic assays. A modified version of the standard MTS assay was established, in which an additional step was added replacing the test medium, containing hydralazine, with fresh culture medium immediately before the addition of the MTS reagent. Culture with hydralazine at concentrations of 50, 100, and 500 mu M for 2 h increased absorbance (p< 0.05) in the standard MTS assay, whereas microscopy suggested no change in cell numbers. Culture with 500 mu m hydralazine for 24 h increased absorbance (p< 0.05) in the standard MTS assay, however, trypan blue exclusion and microscopy suggested a decrease in cell numbers. In a cell-free system, hydralazine (>= 10 mu M) increased absorbance in a concentration-dependent manner. The modified MTS assay produced results consistent with trypan blue exclusion and microscopy. In conclusion, a simple modification of the standard MTS assay overcame the interference of hydralazine and may be useful to avoid interference from other tested compounds.
- Authors: Wang, Yutang , Nguyen, Dinh , Yang, Guang , Anesi, Jack , Chai, Zhonglin , Charchar, Fadi , Golledge, Jonathan
- Date: 2020
- Type: Text , Journal article
- Relation: Assay and Drug Development Technologies Vol. 18, no. 8 (Dec 2020), p. 379-384
- Relation: https://purl.org/au-research/grants/nhmrc/1062671
- Full Text:
- Reviewed:
- Description: The MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium] assay is one of the most commonly used assays to assess cell proliferation and cytotoxicity, but is subject to interference by testing compounds. Hydralazine, an antihypertensive drug, is commonly investigated in multiple fields such as heart failure, cancer, and blood pressure research. This study reported interference of the MTS assay by hydralazine and a simple modification overcoming this interference. Vascular smooth muscle cells were cultured in the presence or absence of hydralazine (0, 10, 50,100, and 500 mu M) for 2 or 24 h. Cell numbers were analyzed using MTS, trypan blue exclusion, or microscopic assays. A modified version of the standard MTS assay was established, in which an additional step was added replacing the test medium, containing hydralazine, with fresh culture medium immediately before the addition of the MTS reagent. Culture with hydralazine at concentrations of 50, 100, and 500 mu M for 2 h increased absorbance (p< 0.05) in the standard MTS assay, whereas microscopy suggested no change in cell numbers. Culture with 500 mu m hydralazine for 24 h increased absorbance (p< 0.05) in the standard MTS assay, however, trypan blue exclusion and microscopy suggested a decrease in cell numbers. In a cell-free system, hydralazine (>= 10 mu M) increased absorbance in a concentration-dependent manner. The modified MTS assay produced results consistent with trypan blue exclusion and microscopy. In conclusion, a simple modification of the standard MTS assay overcame the interference of hydralazine and may be useful to avoid interference from other tested compounds.
Angiotensin converting enzyme 2 and atherosclerosis
- Wang, Yutang, Tikellis, Chris, Thomas, Merlin, Golledge, Jonathan
- Authors: Wang, Yutang , Tikellis, Chris , Thomas, Merlin , Golledge, Jonathan
- Date: 2013
- Type: Text , Journal article , Review
- Relation: Atherosclerosis Vol. 226, no. 1 (2013), p. 3-8
- Full Text: false
- Reviewed:
- Description: Angiotensin converting enzyme 2 (ACE2) is a homolog of angiotensin converting enzyme (ACE) which generates angiotensin II from angiotensin I. ACE, its product angiotensin II and the downstream angiotensin type I receptor are important components of the renin-angiotensin system (RAS). Angiotensin II, the most important component of the RAS, promotes the development of atherosclerosis. The identification of ACE2 in 2000 opened a new chapter of research on the regulation of the RAS. ACE2 degrades pro-atherosclerotic angiotensin II and generates anti-atherosclerotic angiotensin 1-7. In this review, we explored the importance of ACE2 in protecting experimental animals from developing atherosclerosis and its involvement in human atherosclerosis. We also examined the published evidence assessing the importance of ACE2 in different cell types relevant to atherosclerosis and putative underlying cellular and molecular mechanisms linking ACE2 with protection from atherosclerosis. ACE2 shifts the balance from angiotensin II to angiotensin 1-7 inhibiting the progression of atherosclerosis in animal models. © 2012 Elsevier Ireland Ltd.
Angiotensin II, Sympathetic nerve activity and chronic heart failure
- Wang, Yutang, Seto, Sai-Wang, Golledge, Jonathan
- Authors: Wang, Yutang , Seto, Sai-Wang , Golledge, Jonathan
- Date: 2014
- Type: Text , Journal article
- Relation: Heart Failure Reviews Vol. 19, no. 2 (2014), p. 187-198
- Full Text: false
- Reviewed:
- Description: Sympathetic nerve activity has been reported to be increased in both humans and animals with chronic heart failure. One of the mechanisms believed to be responsible for this phenomenon is increased systemic and cerebral angiotensin II signaling. Plasma angiotensin II is increased in humans and animals with chronic heart failure. The increase in angiotensin II signaling enhances sympathetic nerve activity through actions on both central and peripheral sites during chronic heart failure. Angiotensin II signaling is enhanced in different brain sites such as the paraventricular nucleus, the rostral ventrolateral medulla and the area postrema. Blocking angiotensin II type 1 receptors decreases sympathetic nerve activity and cardiac sympathetic afferent reflex when therapy is administered to the paraventricular nucleus. Injection of an angiotensin receptor blocker into the area postrema activates the sympathoinhibitory baroreflex. In peripheral regions, angiotensin II elevates both norepinephrine release and synthesis and inhibits norepinephrine uptake at nerve endings, which may contribute to the increase in sympathetic nerve activity seen in chronic heart failure. Increased circulating angiotensin II during chronic heart failure may enhance the sympathoexcitatory chemoreflex and inhibit the sympathoinhibitory baroreflex. In addition, increased circulating angiotensin II can directly act on the central nervous system via the subfornical organ and the area postrema to increase sympathetic outflow. Inhibition of angiotensin II formation and its type 1 receptor has been shown to have beneficial effects in chronic heart failure patients. © 2012 Springer Science+Business Media New York.
Hypouricemia is a risk factor for diabetes in Chinese adults
- Wang, Yutang, Shao, Yanan, Qian, Tingting, Sun, Hui, Xu, Qun, Hou, Xujuan, Hu, Wenqi, Zhang, Guang, Song, David, Fang, Yan, Magliano, Dianna, Witting, Paul, Golledge, Jonathan, Yang, Guang
- Authors: Wang, Yutang , Shao, Yanan , Qian, Tingting , Sun, Hui , Xu, Qun , Hou, Xujuan , Hu, Wenqi , Zhang, Guang , Song, David , Fang, Yan , Magliano, Dianna , Witting, Paul , Golledge, Jonathan , Yang, Guang
- Date: 2022
- Type: Text , Journal article
- Relation: Obesity Medicine Vol. 31, no. (2022), p.
- Full Text: false
- Reviewed:
- Description: Aims: It is unknown whether low serum uric acid (hypouricemia) is associated with diabetes diagnosis. This study aimed to investigate this association in Chinese adults. Methods: This cross-sectional study included 22,546 Chinese adults. The reference interval for serum uric acid was determined in a sub-group of healthy individuals. The association between hypouricemia and diabetes was analyzed using binary logistic regression. Results: The serum uric acid reference intervals were 3.78–8.31 mg/dL for males and 2.76–6.24 mg/dL for females. Hypouricemia was defined as serum uric acid concentration <3.78 mg/dL for males and <2.76 mg/dL for females. Hypouricemia was associated with an increased likelihood of diabetes diagnosis in both unadjusted (odds ratio [OR], 2.23; 95% confidence interval [CI], 1.78–2.79) and risk factor adjusted (OR, 2.67; 95% CI, 2.08–3.43) analyses. In a sub-group analysis, hypouricemia was significantly independently associated with an increased likelihood of diabetes diagnosis in males but not females. Conclusion: This study suggests that hypouricemia is independently associated with an increased risk of diabetes diagnosis. The findings should be validated in prospective cohort studies. © 2022 Elsevier Ltd
microRNA profiling in patients with abdominal aortic aneurysms: the significance of miR-155
- Biros, Erik, Moran, Corey, Wang, Yutang, Walker, Philip, Cardinal, John, Golledge, Jonathan
- Authors: Biros, Erik , Moran, Corey , Wang, Yutang , Walker, Philip , Cardinal, John , Golledge, Jonathan
- Date: 2014
- Type: Text , Journal article
- Relation: Clinical Science Vol. 126, no. 11 (2014), p. 795
- Full Text: false
- Reviewed:
- Description: AAA (abdominal aortic aneurysm) is a potentially life-threatening late-onset degenerative condition. miRNAs (microRNAs), the small non-coding RNA molecules that regulate gene expression, have been shown previously to be associated with a broad range of human pathologies, including cardiovascular diseases. The aim of the present study was to identify AAA-associated miRNAs potentially contributing to AAA pathology. We analysed the expression of 124 miRNAs within AAA biopsies and serum of ten patients undergoing AAA repair, and serum from ten age- and sex-matched subjects without AAA, using the FlexmiR™ MicroRNA Assay. RNA extracted from the site of main AAA dilatation (AAA body) was compared with that extracted from the macroscopically non-dilated neck of the AAA (AAA neck). Similarly, RNA extracted from the serum of AAA patients (AAA serum) was compared with that extracted from age- and sex-matched controls (control serum). qPCR (quantitative real-time PCR), Western blot analysis and histology were performed using an independent set of six paired AAA body and neck biopsies to examine the validity of findings. Seven miRNAs were up-regulated [>2-fold difference, FDR (false discovery rate) <0.5] within AAA biopsies, of which miR-155 was the most differentially expressed (11.32-fold, FDR=0.414). This finding was confirmed by qPCR with the median relative expression of miR-155 being 3.26 and 0.63 within AAA body and AAA neck biopsies respectively (P=0.031). Circulating miR-155 was also increased in AAA patients compared with controls, with a 2.67-fold up-regulation at borderline significance (FDR=0.554). Two immunologically important miR-155 target genes, CTLA4 (cytotoxic T-lymphocyte-associated protein) and SMAD2, were assessed and found to be significantly down-regulated within AAA bodies compared with AAA necks (P=0.032 and P=0.026) as determined by qPCR and Western blotting respectively. Histology demonstrated dense accumulation of T-lymphocytes within the adventitial and outer medial layers of AAA body, but not neck tissue. The results of the present study suggest that miR-155 is overexpressed in AAA with potential implications in the pathogenesis of the condition.
Mouse models for abdominal aortic aneurysm
- Golledge, Jonathan, Krishna, Smriti, Wang, Yutang
- Authors: Golledge, Jonathan , Krishna, Smriti , Wang, Yutang
- Date: 2022
- Type: Text , Journal article , Review
- Relation: British Journal of Pharmacology Vol. 179, no. 5 (2022), p. 792-810
- Full Text:
- Reviewed:
- Description: Abdominal aortic aneurysm (AAA) rupture is estimated to cause 200,000 deaths each year. Currently, the only treatment for AAA is surgical repair; however, this is only indicated for large asymptomatic, symptomatic or ruptured aneurysms, is not always durable, and is associated with a risk of serious perioperative complications. As a result, patients with small asymptomatic aneurysms or who are otherwise unfit for surgery are treated conservatively, but up to 70% of small aneurysms continue to grow, increasing the risk of rupture. There is thus an urgent need to develop drug therapies effective at slowing AAA growth. This review describes the commonly used mouse models for AAA. Recent research in these models highlights key roles for pathways involved in inflammation and cell turnover in AAA pathogenesis. There is also evidence for long non-coding RNAs and thrombosis in aneurysm pathology. Further well-designed research in clinically relevant models is expected to be translated into effective AAA drugs. LINKED ARTICLES: This article is part of a themed issue on Preclinical Models for Cardiovascular disease research (BJP 75th Anniversary). To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.5/issuetoc. © 2020 The British Pharmacological Society
- Authors: Golledge, Jonathan , Krishna, Smriti , Wang, Yutang
- Date: 2022
- Type: Text , Journal article , Review
- Relation: British Journal of Pharmacology Vol. 179, no. 5 (2022), p. 792-810
- Full Text:
- Reviewed:
- Description: Abdominal aortic aneurysm (AAA) rupture is estimated to cause 200,000 deaths each year. Currently, the only treatment for AAA is surgical repair; however, this is only indicated for large asymptomatic, symptomatic or ruptured aneurysms, is not always durable, and is associated with a risk of serious perioperative complications. As a result, patients with small asymptomatic aneurysms or who are otherwise unfit for surgery are treated conservatively, but up to 70% of small aneurysms continue to grow, increasing the risk of rupture. There is thus an urgent need to develop drug therapies effective at slowing AAA growth. This review describes the commonly used mouse models for AAA. Recent research in these models highlights key roles for pathways involved in inflammation and cell turnover in AAA pathogenesis. There is also evidence for long non-coding RNAs and thrombosis in aneurysm pathology. Further well-designed research in clinically relevant models is expected to be translated into effective AAA drugs. LINKED ARTICLES: This article is part of a themed issue on Preclinical Models for Cardiovascular disease research (BJP 75th Anniversary). To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.5/issuetoc. © 2020 The British Pharmacological Society
Mouse models of intracranial aneurysm
- Wang, Yutang, Emeto, Theophilus, Lee, James, Marshman, Laurence, Moran, Corey, Seto, Sai-wang, Golledge, Jonathan
- Authors: Wang, Yutang , Emeto, Theophilus , Lee, James , Marshman, Laurence , Moran, Corey , Seto, Sai-wang , Golledge, Jonathan
- Date: 2014
- Type: Text , Journal article
- Relation: Brain Pathology Vol. 25, no. (2014), p. 237-247
- Relation: http://purl.org/au-research/grants/nhmrc/1062671
- Full Text: false
- Reviewed:
- Description: Subarachnoid hemorrhage secondary to rupture of an intracranial aneurysm is a highly lethal medical condition. Current management strategies for unruptured intracranial aneurysms involve radiological surveillance and neurosurgical or endovascular interventions. There is no pharmacological treatment available to decrease the risk of aneurysm rupture and subsequent subarachnoid hemorrhage. There is growing interest in the pathogenesis of intracranial aneurysm focused on the development of drug therapies to decrease the incidence of aneurysm rupture. The study of rodent models of intracranial aneurysms has the potential to improve our understanding of intracranial aneurysm development and progression. This review summarizes current mouse models of intact and ruptured intracranial aneurysms and discusses the relevance of these models to human intracranial aneurysms. The article also reviews the importance of these models in investigating the molecular mechanisms involved in the disease. Finally, potential pharmaceutical targets for intracranial aneurysm suggested by previous studies are discussed. Examples of potential drug targets include matrix metalloproteinases, stromal cell-derived factor-1, tumor necrosis factor-α, the renin-angiotensin system and the β-estrogen receptor. An agreed clear, precise and reproducible definition of what constitutes an aneurysm in the models would assist in their use to better understand the pathology of intracranial aneurysm and applying findings to patients
- Description: Subarachnoid hemorrhage secondary to rupture of an intracranial aneurysm is a highly lethal medical condition. Current management strategies for unruptured intracranial aneurysms involve radiological surveillance and neurosurgical or endovascular interventions. There is no pharmacological treatment available to decrease the risk of aneurysm rupture and subsequent subarachnoid hemorrhage. There is growing interest in the pathogenesis of intracranial aneurysm focused on the development of drug therapies to decrease the incidence of aneurysm rupture. The study of rodent models of intracranial aneurysms has the potential to improve our understanding of intracranial aneurysm development and progression. This review summarizes current mouse models of intact and ruptured intracranial aneurysms and discusses the relevance of these models to human intracranial aneurysms. The article also reviews the importance of these models in investigating the molecular mechanisms involved in the disease. Finally, potential pharmaceutical targets for intracranial aneurysm suggested by previous studies are discussed. Examples of potential drug targets include matrix metalloproteinases, stromal cell-derived factor-1, tumor necrosis factor-
Parenteral administration of factor Xa/IIa inhibitors limits experimental aortic aneurysm and atherosclerosis
- Moran, Corey, Seto, Sai-Wang, Krishna, Smriti, Sharma, Surabhi, Jose, Roby, Biros, Erik, Wang, Yutang, Morton, Susan, Golledge, Jonathan
- Authors: Moran, Corey , Seto, Sai-Wang , Krishna, Smriti , Sharma, Surabhi , Jose, Roby , Biros, Erik , Wang, Yutang , Morton, Susan , Golledge, Jonathan
- Date: 2017
- Type: Text , Journal article
- Relation: Scientific Reports Vol. 7, no. (2017), p. 1-12
- Full Text:
- Reviewed:
- Description: Intraluminal thrombus is a consistent feature of human abdominal aortic aneurysm (AAA). Coagulation factor Xa (FXa) catalyses FII to thrombin (FIIa). We examined the effect of FXa/FIIa inhibition on experimental aortic aneurysm in apolipoprotein E-deficient (ApoE '/') mice infused with angiotensin II (AngII). The concentration of FXa within the supra-renal aorta (SRA) correlated positively with SRA diameter. Parenteral administration of enoxaparin (FXa/IIa inhibitor) and fondaparinux (FXa inhibitor) over 14 days reduced to severity of aortic aneurysm and atherosclerosis in AngII-infused ApoE '/' mice. Enteral administration of the FIIa inhibitor dabigatran had no significant effect. Aortic protease-activated receptor (PAR)-2 expression increased in response to AngII infusion. Fondaparinux reduced SRA levels of FXa, FIIa, PAR-2, matrix metalloproteinase (MMP)2, Smad2/3 phosphorylation, and MOMA-2 positive cells in the mouse model. FXa stimulated Smad2/3 phosphorylation and MMP2 expression in aortic vascular smooth muscle cells (VSMC) in vitro. Expression of MMP2 in FXa-stimulated VSMC was downregulated in the presence of a PAR-2 but not a PAR-1 inhibitor. These findings suggest that FXa/FIIa inhibition limits aortic aneurysm and atherosclerosis severity due to down-regulation of vascular PAR-2-mediated Smad2/3 signalling and MMP2 expression. Inhibition of FXa/FIIa may be a potential therapy for limiting aortic aneurysm. © The Author(s) 2017.
- Authors: Moran, Corey , Seto, Sai-Wang , Krishna, Smriti , Sharma, Surabhi , Jose, Roby , Biros, Erik , Wang, Yutang , Morton, Susan , Golledge, Jonathan
- Date: 2017
- Type: Text , Journal article
- Relation: Scientific Reports Vol. 7, no. (2017), p. 1-12
- Full Text:
- Reviewed:
- Description: Intraluminal thrombus is a consistent feature of human abdominal aortic aneurysm (AAA). Coagulation factor Xa (FXa) catalyses FII to thrombin (FIIa). We examined the effect of FXa/FIIa inhibition on experimental aortic aneurysm in apolipoprotein E-deficient (ApoE '/') mice infused with angiotensin II (AngII). The concentration of FXa within the supra-renal aorta (SRA) correlated positively with SRA diameter. Parenteral administration of enoxaparin (FXa/IIa inhibitor) and fondaparinux (FXa inhibitor) over 14 days reduced to severity of aortic aneurysm and atherosclerosis in AngII-infused ApoE '/' mice. Enteral administration of the FIIa inhibitor dabigatran had no significant effect. Aortic protease-activated receptor (PAR)-2 expression increased in response to AngII infusion. Fondaparinux reduced SRA levels of FXa, FIIa, PAR-2, matrix metalloproteinase (MMP)2, Smad2/3 phosphorylation, and MOMA-2 positive cells in the mouse model. FXa stimulated Smad2/3 phosphorylation and MMP2 expression in aortic vascular smooth muscle cells (VSMC) in vitro. Expression of MMP2 in FXa-stimulated VSMC was downregulated in the presence of a PAR-2 but not a PAR-1 inhibitor. These findings suggest that FXa/FIIa inhibition limits aortic aneurysm and atherosclerosis severity due to down-regulation of vascular PAR-2-mediated Smad2/3 signalling and MMP2 expression. Inhibition of FXa/FIIa may be a potential therapy for limiting aortic aneurysm. © The Author(s) 2017.
Reduced renal function may explain the higher prevalence of hyperuricemia in older people
- Wang, Yutang, Zhang, Wanlin, Qian, Tingting, Sun, Hui, Xu, Qun, Hou, Xujuan, Hu, Wenqi, Zhang, Guang, Drummond, Grant, Sobey, Chris, Charchar, Fadi, Golledge, Jonathan, Yang, Guang
- Authors: Wang, Yutang , Zhang, Wanlin , Qian, Tingting , Sun, Hui , Xu, Qun , Hou, Xujuan , Hu, Wenqi , Zhang, Guang , Drummond, Grant , Sobey, Chris , Charchar, Fadi , Golledge, Jonathan , Yang, Guang
- Date: 2021
- Type: Text , Journal article
- Relation: Scientific Reports Vol. 11, no. 1 (2021), p.
- Relation: https://purl.org/au-research/grants/nhmrc/1062671
- Full Text:
- Reviewed:
- Description: This study aimed to investigate the contribution of renal dysfunction to enhanced hyperuricemia prevalence in older people. A cohort of 13,288 Chinese people aged between 40 and 95 years were recruited from January to May 2019. Serum uric acid concentration and estimated glomerular filtration rate [eGFR] were measured. The associations between age or eGFR and serum uric acid or hyperuricemia were analyzed using linear or binary logistic regression adjusting for risk factors. Uric acid concentration and prevalence of hyperuricemia were greater in older participants. Adjustment for reduced renal function (eGFR < 60 mL/min/1.73 m2) eliminated the associations between older age and higher uric acid concentration and between older age and higher prevalence of hyperuricemia diagnosis, whereas adjustment for other risk factors did not change those associations. Lower eGFR was associated with higher uric acid concentration both before (β = − 0.296, P < 0.001) and after adjustment for age (β = − 0.313, P < 0.001). Reduced renal function was associated with hyperuricemia diagnosis both before (odds ratio, OR, 3.64; 95% CI 3.10–4.28; P < 0.001) and after adjustment for age (adjusted OR, 3.82; 95% CI 3.22–4.54; P < 0.001). Mean serum uric acid and prevalence of hyperuricemia were higher in people with eGFR < 60 mL/min/1.73 m2 than those with eGFR ≥ 60 mL/min/1.73 m2. The prevalence of reduced renal function increased with older age (P < 0.001). This study suggests that reduced renal function can explain the increased uric acid levels and hyperuricemia diagnoses in older people. © 2021, The Author(s).
- Authors: Wang, Yutang , Zhang, Wanlin , Qian, Tingting , Sun, Hui , Xu, Qun , Hou, Xujuan , Hu, Wenqi , Zhang, Guang , Drummond, Grant , Sobey, Chris , Charchar, Fadi , Golledge, Jonathan , Yang, Guang
- Date: 2021
- Type: Text , Journal article
- Relation: Scientific Reports Vol. 11, no. 1 (2021), p.
- Relation: https://purl.org/au-research/grants/nhmrc/1062671
- Full Text:
- Reviewed:
- Description: This study aimed to investigate the contribution of renal dysfunction to enhanced hyperuricemia prevalence in older people. A cohort of 13,288 Chinese people aged between 40 and 95 years were recruited from January to May 2019. Serum uric acid concentration and estimated glomerular filtration rate [eGFR] were measured. The associations between age or eGFR and serum uric acid or hyperuricemia were analyzed using linear or binary logistic regression adjusting for risk factors. Uric acid concentration and prevalence of hyperuricemia were greater in older participants. Adjustment for reduced renal function (eGFR < 60 mL/min/1.73 m2) eliminated the associations between older age and higher uric acid concentration and between older age and higher prevalence of hyperuricemia diagnosis, whereas adjustment for other risk factors did not change those associations. Lower eGFR was associated with higher uric acid concentration both before (β = − 0.296, P < 0.001) and after adjustment for age (β = − 0.313, P < 0.001). Reduced renal function was associated with hyperuricemia diagnosis both before (odds ratio, OR, 3.64; 95% CI 3.10–4.28; P < 0.001) and after adjustment for age (adjusted OR, 3.82; 95% CI 3.22–4.54; P < 0.001). Mean serum uric acid and prevalence of hyperuricemia were higher in people with eGFR < 60 mL/min/1.73 m2 than those with eGFR ≥ 60 mL/min/1.73 m2. The prevalence of reduced renal function increased with older age (P < 0.001). This study suggests that reduced renal function can explain the increased uric acid levels and hyperuricemia diagnoses in older people. © 2021, The Author(s).
Renal denervation promotes atherosclerosis in hypertensive apolipoprotein E-Deficient mice infused with angiotensin II
- Wang, Yutang, Dinh, Tam, Nield, Alex, Krishna, Smriti, Denton, Kate, Golledge, Jonathan
- Authors: Wang, Yutang , Dinh, Tam , Nield, Alex , Krishna, Smriti , Denton, Kate , Golledge, Jonathan
- Date: 2017
- Type: Text , Journal article
- Relation: Frontiers in Physiology Vol. 8, no. (2017), p. 1-9
- Relation: http://purl.org/au-research/grants/nhmrc/1062671
- Full Text:
- Reviewed:
- Description: Objective: To determine the effect of renal denervation (RDN) on the severity of atherosclerosis and aortic aneurysm in hypertensive mice. Methods: Hypertension, atherosclerosis and aortic aneurysm were induced by subcutaneous infusion of angiotensin II (1 μg/kg/min) for 28 days in apolipoprotein E-deficient mice. RDN was conducted using combined surgical and local chemical denervation. The norepinephrine concentration in the kidney was measured by high-performance liquid chromatography. Blood pressure was measured by the tail-cuff method. Atherosclerosis was assessed by Sudan IV staining of the aortic arch. The aortic diameter was measured by the morphometric method. The mRNA expression of genes associated with atherosclerosis and aortic aneurysm were analyzed by quantitative PCR. Results: RDN decreased the median norepinephrine content in the kidney by 93.4% (n = 5-7, P = 0.003) 5 days after the procedure, indicating that the RDN procedure was successful. RDN decreased systolic blood pressure in apolipoprotein E-deficient mice. Mice that had RDN had more severe aortic arch atherosclerosis (median percentage of Sudan IV positive area: 13.2% in control mice, n = 12, and 25.4% in mice having RDN, n = 12, P = 0.028). The severity of the atherosclerosis was negatively correlated with the renal norepinephrine content (spearman r = -0.6557, P = 0.005). RDN did not affect the size of aortic aneurysms formed or the incidence of aortic rupture in mice receiving angiotensin II. RDN significantly increased the aortic mRNA expression of matrix metalloproteinase-2 (MMP-2). Conclusion: RDN promoted atherosclerosis in apolipoprotein E-deficient mice infused with angiotensin II associated with upregulation of MMP-2. The higher MMP-2 expression could be the results of the greater amount of atheroma in the RDN mice. The findings suggest further research is needed to assess potentially deleterious effects of RDN in patients. © 2017 Wang, Dinh, Nield, Krishna, Denton and Golledge.
- Authors: Wang, Yutang , Dinh, Tam , Nield, Alex , Krishna, Smriti , Denton, Kate , Golledge, Jonathan
- Date: 2017
- Type: Text , Journal article
- Relation: Frontiers in Physiology Vol. 8, no. (2017), p. 1-9
- Relation: http://purl.org/au-research/grants/nhmrc/1062671
- Full Text:
- Reviewed:
- Description: Objective: To determine the effect of renal denervation (RDN) on the severity of atherosclerosis and aortic aneurysm in hypertensive mice. Methods: Hypertension, atherosclerosis and aortic aneurysm were induced by subcutaneous infusion of angiotensin II (1 μg/kg/min) for 28 days in apolipoprotein E-deficient mice. RDN was conducted using combined surgical and local chemical denervation. The norepinephrine concentration in the kidney was measured by high-performance liquid chromatography. Blood pressure was measured by the tail-cuff method. Atherosclerosis was assessed by Sudan IV staining of the aortic arch. The aortic diameter was measured by the morphometric method. The mRNA expression of genes associated with atherosclerosis and aortic aneurysm were analyzed by quantitative PCR. Results: RDN decreased the median norepinephrine content in the kidney by 93.4% (n = 5-7, P = 0.003) 5 days after the procedure, indicating that the RDN procedure was successful. RDN decreased systolic blood pressure in apolipoprotein E-deficient mice. Mice that had RDN had more severe aortic arch atherosclerosis (median percentage of Sudan IV positive area: 13.2% in control mice, n = 12, and 25.4% in mice having RDN, n = 12, P = 0.028). The severity of the atherosclerosis was negatively correlated with the renal norepinephrine content (spearman r = -0.6557, P = 0.005). RDN did not affect the size of aortic aneurysms formed or the incidence of aortic rupture in mice receiving angiotensin II. RDN significantly increased the aortic mRNA expression of matrix metalloproteinase-2 (MMP-2). Conclusion: RDN promoted atherosclerosis in apolipoprotein E-deficient mice infused with angiotensin II associated with upregulation of MMP-2. The higher MMP-2 expression could be the results of the greater amount of atheroma in the RDN mice. The findings suggest further research is needed to assess potentially deleterious effects of RDN in patients. © 2017 Wang, Dinh, Nield, Krishna, Denton and Golledge.
- Moran, Corey, Biros, Erik, Krishna, Smriti, Wang, Yutang, Tikellis, Chris, Moxon, Joseph, Cooper, Mark, Norman, Paul, Burrell, Louise, Thomas, Merlin, Golledge, Jonathan
- Authors: Moran, Corey , Biros, Erik , Krishna, Smriti , Wang, Yutang , Tikellis, Chris , Moxon, Joseph , Cooper, Mark , Norman, Paul , Burrell, Louise , Thomas, Merlin , Golledge, Jonathan
- Date: 2017
- Type: Text , Journal article
- Relation: Arteriosclerosis Thrombosis and Vascular Biology Vol. 37, no. 11 (2017), p. 2195-2203
- Full Text: false
- Reviewed:
- Description: Objective-Recent evidence suggests an important role for angiotensin-converting enzyme 2 (ACE2) in limiting abdominal aortic aneurysm (AAA). This study examined the effect of ACE2 deficiency on AAA development and the efficacy of resveratrol to upregulate ACE2 in experimental AAA. Approach and Results-Ace2 deletion in apolipoprotein-deficient mice (ApoE(-/-)Ace2(-/y)) resulted in increased aortic diameter and spontaneous aneurysm of the suprarenal aorta associated with increased expression of inflammation and proteolytic enzyme markers. In humans, serum ACE2 activity was negatively associated with AAA diagnosis. ACE2 expression was lower in infrarenal biopsies of patients with AAA than organ donors. AAA was more severe in ApoE (-/-)Ace2(-/y) mice compared with controls in 2 experimental models. Resveratrol (0.05/100-g chow) inhibited growth of pre-established AAAs in ApoE(-/-) mice fed high-fat chow and infused with angiotensin II continuously for 56 days. Reduced suprarenal aorta dilatation in mice receiving resveratrol was associated with elevated serum ACE2 and increased suprarenal aorta tissue levels of ACE2 and sirtuin 1 activity. In addition, the relative phosphorylation of Akt and ERK (extracellular signal-regulated kinase) 1/2 within suprarenal aorta tissue and gene expression for nuclear factor of kappa light polypeptide gene enhancer in B cells 1, angiotensin type-1 receptor, and metallopeptidase 2 and 9 were significantly reduced. Upregulation of ACE2 in human aortic smooth muscle cells by resveratrol in vitro was sirtuin 1-dependent. Conclusions-This study provides experimental evidence of an important role for ACE2 in limiting AAA development and growth. Resveratrol upregulated ACE2 and inhibited AAA growth in a mouse model.
The association between serum uric acid and blood pressure in different age groups in a healthy Chinese cohort
- Cheng, Wenjuan, Wen, Shiling, Wang, Yutang, Qian, Zhiping, Tan, Yuyao, Li, Hongying, Hou, Yueli, Hu, Haiyang, Golledge, Jonathan, Yang, Guang
- Authors: Cheng, Wenjuan , Wen, Shiling , Wang, Yutang , Qian, Zhiping , Tan, Yuyao , Li, Hongying , Hou, Yueli , Hu, Haiyang , Golledge, Jonathan , Yang, Guang
- Date: 2017
- Type: Text , Journal article
- Relation: Medicine (United States) Vol. 96, no. 50 (2017), p.1-6
- Relation: http://purl.org/au-research/grants/nhmrc/1062671
- Full Text:
- Reviewed:
- Description: High serum uric acid (sUA) has been reported to be a risk factor for hypertension however, whether this is the case for all age groups is not clear. We examined the association between sUA concentrations and systolic and diastolic blood pressure (SBP and DBP) in different age groups in a cohort of healthy Chinese participants. A total of 1082 healthy participants aged from 41 to 70 years were included. sUA concentration was measured by the uricase-peroxidase method. SBP and DBP were assessed using mercury sphygmomanometry. Hypertension was defined as SBP ≥140 mm Hg or DBP ≥90 mm Hg. Hyperuricemia (HUA) was defined as sUA concentration of >7 mg/dL in men and >6 mg/dL in women. The association between sUA concentration and SBP and DBP was examined using Pearson's correlation test, multivariate linear regression, and logistic regression analysis. The prevalence of hypertension and HUA increased with age (P < .001). Hypertension was more common in participants that had HUA than in those that did not (38.95% vs 30.16%, P = .02). Higher sUA was significantly associated with higher SBP and DBP in the 41- to 50-year-old participants (SBP, β = 0.35, P < .001; DBP, β = .29, P < .001; after adjustment for age, sex, total cholesterol, estimated glomerular filtration rate, and fasting plasma glucose). HUA was also a risk factor for hypertension in this age group (odds ratio 1.425, 95% confidence interval, 1.217-1.668, P < .001). There was no association between sUA concentration and SBP and DBP in the other age groups. In this population of healthy Chinese participants, sUA concentration was positively associated with hypertension only in the 41- to 50-year-old group. Lowering uric acid in this age group may help to reduce the incidence of hypertension.
- Authors: Cheng, Wenjuan , Wen, Shiling , Wang, Yutang , Qian, Zhiping , Tan, Yuyao , Li, Hongying , Hou, Yueli , Hu, Haiyang , Golledge, Jonathan , Yang, Guang
- Date: 2017
- Type: Text , Journal article
- Relation: Medicine (United States) Vol. 96, no. 50 (2017), p.1-6
- Relation: http://purl.org/au-research/grants/nhmrc/1062671
- Full Text:
- Reviewed:
- Description: High serum uric acid (sUA) has been reported to be a risk factor for hypertension however, whether this is the case for all age groups is not clear. We examined the association between sUA concentrations and systolic and diastolic blood pressure (SBP and DBP) in different age groups in a cohort of healthy Chinese participants. A total of 1082 healthy participants aged from 41 to 70 years were included. sUA concentration was measured by the uricase-peroxidase method. SBP and DBP were assessed using mercury sphygmomanometry. Hypertension was defined as SBP ≥140 mm Hg or DBP ≥90 mm Hg. Hyperuricemia (HUA) was defined as sUA concentration of >7 mg/dL in men and >6 mg/dL in women. The association between sUA concentration and SBP and DBP was examined using Pearson's correlation test, multivariate linear regression, and logistic regression analysis. The prevalence of hypertension and HUA increased with age (P < .001). Hypertension was more common in participants that had HUA than in those that did not (38.95% vs 30.16%, P = .02). Higher sUA was significantly associated with higher SBP and DBP in the 41- to 50-year-old participants (SBP, β = 0.35, P < .001; DBP, β = .29, P < .001; after adjustment for age, sex, total cholesterol, estimated glomerular filtration rate, and fasting plasma glucose). HUA was also a risk factor for hypertension in this age group (odds ratio 1.425, 95% confidence interval, 1.217-1.668, P < .001). There was no association between sUA concentration and SBP and DBP in the other age groups. In this population of healthy Chinese participants, sUA concentration was positively associated with hypertension only in the 41- to 50-year-old group. Lowering uric acid in this age group may help to reduce the incidence of hypertension.
The concentration of ethanol affects its penetration rate in bovine cardiac and hepatic tissues
- Dunster-Jones, Matthew, Steicke, Michelle, Mackie, James, Guthrie, Rachel, Dinh, Tam, Ahmady, Fahima, Golledge, Jonathan, Wang, Yutang
- Authors: Dunster-Jones, Matthew , Steicke, Michelle , Mackie, James , Guthrie, Rachel , Dinh, Tam , Ahmady, Fahima , Golledge, Jonathan , Wang, Yutang
- Date: 2018
- Type: Text , Journal article
- Relation: Folia Histochemica et Cytobiologica Vol. 56, no. 2 (2018), p. 92-97
- Relation: http://purl.org/au-research/grants/nhmrc/1062671
- Full Text:
- Reviewed:
- Description: Introduction. Ethanol is a commonly used fixative. Fixation of the inner layers of the tissue depends on the ability of the fixative to diffuse into the tissue. It is unknown whether the concentration of ethanol affects its penetration into tissues. This study aimed to compare the penetration rates of 50% and 100% ethanol into bovine heart and liver tissues. Materials and methods. The penetration distance and tissue shrinkage or expansion were measured by analysing the digital images of the heart and liver tissues before and after immersion in ethanol at 20°C for 2, 6, 24 or 30 hours. The penetration coefficients were calculated as the slope of the regression line using the linear regression function between the penetration distance and square root of fixation time. Differences in tissue shrinkage or expansion and penetration distance at various time points between the two concentrations of ethanol were analysed using a mixed design ANOVA followed by Bonferroni’s post-hoc test. Results. The penetration distance of 100% ethanol was significantly greater in both heart and liver tissues compared with that of 50% ethanol (n = 4, p < 0.05 for both). 100% ethanol shrank immersed liver tissue significantly more than 50% ethanol (p = 0.002), but the shrinkage of the heart tissue caused by two concentrations of ethanol did not significantly differ (p = 0.054). The greater penetration distance of 100% over 50% ethanol remained unchanged after normalising the penetration distance to the individual tissue’s shrinkage (n = 4, p < 0.001). The mean penetration coefficient of 100% ethanol was significantly greater than 50% ethanol in the heart tissue (0.906 vs. 0.442, p = 0.003) and in the liver tissue (0.988 vs. 0.622, p = 0.028). Conclusions. It was proven that in two types of tissue that substantially differ in histological structures, 100% ethanol penetrated tissue significantly faster than 50% ethanol.
- Authors: Dunster-Jones, Matthew , Steicke, Michelle , Mackie, James , Guthrie, Rachel , Dinh, Tam , Ahmady, Fahima , Golledge, Jonathan , Wang, Yutang
- Date: 2018
- Type: Text , Journal article
- Relation: Folia Histochemica et Cytobiologica Vol. 56, no. 2 (2018), p. 92-97
- Relation: http://purl.org/au-research/grants/nhmrc/1062671
- Full Text:
- Reviewed:
- Description: Introduction. Ethanol is a commonly used fixative. Fixation of the inner layers of the tissue depends on the ability of the fixative to diffuse into the tissue. It is unknown whether the concentration of ethanol affects its penetration into tissues. This study aimed to compare the penetration rates of 50% and 100% ethanol into bovine heart and liver tissues. Materials and methods. The penetration distance and tissue shrinkage or expansion were measured by analysing the digital images of the heart and liver tissues before and after immersion in ethanol at 20°C for 2, 6, 24 or 30 hours. The penetration coefficients were calculated as the slope of the regression line using the linear regression function between the penetration distance and square root of fixation time. Differences in tissue shrinkage or expansion and penetration distance at various time points between the two concentrations of ethanol were analysed using a mixed design ANOVA followed by Bonferroni’s post-hoc test. Results. The penetration distance of 100% ethanol was significantly greater in both heart and liver tissues compared with that of 50% ethanol (n = 4, p < 0.05 for both). 100% ethanol shrank immersed liver tissue significantly more than 50% ethanol (p = 0.002), but the shrinkage of the heart tissue caused by two concentrations of ethanol did not significantly differ (p = 0.054). The greater penetration distance of 100% over 50% ethanol remained unchanged after normalising the penetration distance to the individual tissue’s shrinkage (n = 4, p < 0.001). The mean penetration coefficient of 100% ethanol was significantly greater than 50% ethanol in the heart tissue (0.906 vs. 0.442, p = 0.003) and in the liver tissue (0.988 vs. 0.622, p = 0.028). Conclusions. It was proven that in two types of tissue that substantially differ in histological structures, 100% ethanol penetrated tissue significantly faster than 50% ethanol.
The penetration of methanol into bovine cardiac and hepatic tissues is faster than ethanol and formalin
- Steicke, Michelle, Yang, Guang, Dinh, Tam, Dunster-Jones, Matthew, Sargisson, Owen, Ahmady, Farah, Golledge, Jonathan, Wang, Yutang
- Authors: Steicke, Michelle , Yang, Guang , Dinh, Tam , Dunster-Jones, Matthew , Sargisson, Owen , Ahmady, Farah , Golledge, Jonathan , Wang, Yutang
- Date: 2018
- Type: Text , Journal article
- Relation: European Journal of Histochemistry Vol. 62, no. 1 (2018), p. 98-104
- Relation: http://purl.org/au-research/grants/nhmrc/1062671
- Full Text:
- Reviewed:
- Description: Methanol, ethanol and formalin are commonly used as fixatives to preserve biological tissues from decay in the preparation of histological sections. Fixation of the inner layers of the tissue depends on the ability of the fixative to diffuse into the tissue. It is unknown whether methanol penetrates tissues at similar rates to other fixatives. This study aimed to compare the penetration rates of methanol, ethanol and formalin into bovine heart and liver tissues. The penetration distance and tissue shrinkage or expansion were measured by analysing the digital images of tissue before and after immersion in different fixatives for 1, 2, 6 or 10 h. Data were analysed using two-way ANOVA, followed by Bonferroni’s post-hoc test. The penetration distance of methanol was significantly greater in both heart and liver tissues compared with that of ethanol (N=4, P<0.001). Methanol or ethanol immersion led to similar shrinkage of both tissues (P>0.05). The penetration rate of formalin was similar to that of ethanol in both tissues however it was significantly slower than methanol (N=4, P<0.005 in the heart; P<0.001 in the liver). The mean penetration coefficients of methanol, formalin and ethanol in the heart tissue were 2.609, 1.994 and 1.801, respectively, and 3.012, 2.153 and 2.113, respectively, in the liver tissue. The penetration coefficient of methanol was significantly greater than that of ethanol or formalin in both tissues (P<0.001 for each comparison). In conclusion, methanol penetrates tissue significantly faster than ethanol and formalin.
- Authors: Steicke, Michelle , Yang, Guang , Dinh, Tam , Dunster-Jones, Matthew , Sargisson, Owen , Ahmady, Farah , Golledge, Jonathan , Wang, Yutang
- Date: 2018
- Type: Text , Journal article
- Relation: European Journal of Histochemistry Vol. 62, no. 1 (2018), p. 98-104
- Relation: http://purl.org/au-research/grants/nhmrc/1062671
- Full Text:
- Reviewed:
- Description: Methanol, ethanol and formalin are commonly used as fixatives to preserve biological tissues from decay in the preparation of histological sections. Fixation of the inner layers of the tissue depends on the ability of the fixative to diffuse into the tissue. It is unknown whether methanol penetrates tissues at similar rates to other fixatives. This study aimed to compare the penetration rates of methanol, ethanol and formalin into bovine heart and liver tissues. The penetration distance and tissue shrinkage or expansion were measured by analysing the digital images of tissue before and after immersion in different fixatives for 1, 2, 6 or 10 h. Data were analysed using two-way ANOVA, followed by Bonferroni’s post-hoc test. The penetration distance of methanol was significantly greater in both heart and liver tissues compared with that of ethanol (N=4, P<0.001). Methanol or ethanol immersion led to similar shrinkage of both tissues (P>0.05). The penetration rate of formalin was similar to that of ethanol in both tissues however it was significantly slower than methanol (N=4, P<0.005 in the heart; P<0.001 in the liver). The mean penetration coefficients of methanol, formalin and ethanol in the heart tissue were 2.609, 1.994 and 1.801, respectively, and 3.012, 2.153 and 2.113, respectively, in the liver tissue. The penetration coefficient of methanol was significantly greater than that of ethanol or formalin in both tissues (P<0.001 for each comparison). In conclusion, methanol penetrates tissue significantly faster than ethanol and formalin.
Wnt signaling pathway inhibitor Sclerostin inhibits angiotensin II-induced aortic aneurysm and atherosclerosis
- Krishna, Smriti, Seto, Sai-Wang, Jose, Roby, Li, Jiaze, Morton, Susan, Biros, Erik, Wang, Yutang, Nsengiyumva, Vianne, Lindeman, Jan, Loots, Gabriela, Rush, Catherine, Craig, Jeffrey, Golledge, Jonathan
- Authors: Krishna, Smriti , Seto, Sai-Wang , Jose, Roby , Li, Jiaze , Morton, Susan , Biros, Erik , Wang, Yutang , Nsengiyumva, Vianne , Lindeman, Jan , Loots, Gabriela , Rush, Catherine , Craig, Jeffrey , Golledge, Jonathan
- Date: 2017
- Type: Text , Journal article
- Relation: Arteriosclerosis Thrombosis and Vascular Biology Vol. 37, no. 3 (2017), p. 553-566
- Full Text:
- Reviewed:
- Description: Objective-Sclerostin (SOST) has been identified as an important regulator of bone formation; however, it has not been previously implicated in arterial disease. The aim of this study was to assess the role of SOST in aortic aneurysm (AA) and atherosclerosis using human samples, a mouse model, and in vitro investigations. Approach and Results-SOST protein was downregulated in human and mouse AA samples compared with controls. Transgenic introduction of human SOST in apolipoprotein E-deficient (ApoE(-/-)) mice (SOSTTg. ApoE(-/-)) and administration of recombinant mouse Sost inhibited angiotensin II-induced AA and atherosclerosis. Serum concentrations of several proinflammatory cytokines were significantly reduced in SOSTTg. ApoE(-/-) mice. Compared with controls, the aortas of mice receiving recombinant mouse Sost and SOSTTg. ApoE(-/-) mice showed reduced matrix degradation, reduced elastin breaks, and preserved collagen. Decreased inflammatory cell infiltration and a reduction in the expression of wingless-type mouse mammary virus integration site/beta-catenin responsive genes, including matrix metalloproteinase-9, osteoprotegerin, and osteopontin, were observed in the aortas of SOSTTg. ApoE(-/-) mice. SOST expression was downregulated and the winglesstype mouse mammary virus integration site/beta-catenin pathway was activated in human AA samples. The cytosinephosphate- guanine islands in the SOST gene promoter showed significantly higher methylation in human AA samples compared with controls. Incubation of vascular smooth muscle cells with the demethylating agent 5-azacytidine resulted in upregulation of SOST, suggesting that SOST is epigenetically regulated. Conclusions-This study identifies that SOST is expressed in the aorta and downregulated in human AA possibly because of epigenetic silencing. Upregulating SOST inhibits AA and atherosclerosis development, with potential important implications for treating these vascular diseases.
- Authors: Krishna, Smriti , Seto, Sai-Wang , Jose, Roby , Li, Jiaze , Morton, Susan , Biros, Erik , Wang, Yutang , Nsengiyumva, Vianne , Lindeman, Jan , Loots, Gabriela , Rush, Catherine , Craig, Jeffrey , Golledge, Jonathan
- Date: 2017
- Type: Text , Journal article
- Relation: Arteriosclerosis Thrombosis and Vascular Biology Vol. 37, no. 3 (2017), p. 553-566
- Full Text:
- Reviewed:
- Description: Objective-Sclerostin (SOST) has been identified as an important regulator of bone formation; however, it has not been previously implicated in arterial disease. The aim of this study was to assess the role of SOST in aortic aneurysm (AA) and atherosclerosis using human samples, a mouse model, and in vitro investigations. Approach and Results-SOST protein was downregulated in human and mouse AA samples compared with controls. Transgenic introduction of human SOST in apolipoprotein E-deficient (ApoE(-/-)) mice (SOSTTg. ApoE(-/-)) and administration of recombinant mouse Sost inhibited angiotensin II-induced AA and atherosclerosis. Serum concentrations of several proinflammatory cytokines were significantly reduced in SOSTTg. ApoE(-/-) mice. Compared with controls, the aortas of mice receiving recombinant mouse Sost and SOSTTg. ApoE(-/-) mice showed reduced matrix degradation, reduced elastin breaks, and preserved collagen. Decreased inflammatory cell infiltration and a reduction in the expression of wingless-type mouse mammary virus integration site/beta-catenin responsive genes, including matrix metalloproteinase-9, osteoprotegerin, and osteopontin, were observed in the aortas of SOSTTg. ApoE(-/-) mice. SOST expression was downregulated and the winglesstype mouse mammary virus integration site/beta-catenin pathway was activated in human AA samples. The cytosinephosphate- guanine islands in the SOST gene promoter showed significantly higher methylation in human AA samples compared with controls. Incubation of vascular smooth muscle cells with the demethylating agent 5-azacytidine resulted in upregulation of SOST, suggesting that SOST is epigenetically regulated. Conclusions-This study identifies that SOST is expressed in the aorta and downregulated in human AA possibly because of epigenetic silencing. Upregulating SOST inhibits AA and atherosclerosis development, with potential important implications for treating these vascular diseases.
- «
- ‹
- 1
- ›
- »