Renal Mechanisms of Association between Fibroblast Growth Factor 1 and Blood Pressure
- Authors: Tomaszewski, Maciej , Eales, James , Denniff, Matthew , Myers, Stephen , Chew, Guatsiew , Nelson, Christopher , Christofidou, Paraskevi , Desai, Aishwarya , Büsst, Cara , Wojnar, Lukasz , Musialik, Katarzyna , Jozwiak, Jacek , Debiec, Radoslaw , Dominiczak, Anna , Navis, Gerjan , van Gilst, Wiek , van der Harst, Pim , Samani, Nilesh , Harrap, Stephen , Bogdanski, Pawel , Zukowska-Szczechowska, Ewa , Charchar, Fadi
- Date: 2015
- Type: Text , Journal article
- Relation: Journal of the American Society of Nephrology Vol. 26, no. 12 (2015), p. 3151-3160
- Relation: http://purl.org/au-research/grants/nhmrc/1009490
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- Description: The fibroblast growth factor 1 (FGF1) gene is expressed primarily in the kidney and may contribute to hypertension. However, the biologic mechanisms underlying the association between FGF1 and BP regulation remain unknown. We report that the major allele of FGF1 single nucleotide polymorphism rs152524 was associated in a dose-dependent manner with systolic BP (P=9.65 x10(-5)) and diastolic BP (P=7.61 x10(-3)) in a meta-analysis of 14,364 individuals and with renal expression of FGF1 mRNA in 126 human kidneys (P=9.0x10(-3)). Next-generation RNA sequencing revealed that upregulated renal expression of FGF1 or of each of the three FGF1 mRNA isoforms individually was associated with higher BP. FGF1-stratified coexpression analysis in two separate collections of human kidneys identified 126 FGF1 partner mRNAs, of which 71 and 63 showed at least nominal association with systolic and diastolic BP, respectively. Of those mRNAs, seven mRNAs in five genes (MME, PTPRO, REN, SLC12A3, and WNK1) had strong prior annotation to BP or hypertension. MME, which encodes an enzyme that degrades circulating natriuretic peptides, showed the strongest differential coexpression with FGF1 between hypertensive and normotensive kidneys. Furthermore, higher level of renal FGF1 expression was associated with lower circulating levels of atrial and brain natriuretic peptides. These findings indicate that FGF1 expression in the kidney is at least under partial genetic control and that renal expression of several FGF1 partner genes involved in the natriuretic peptide catabolism pathway, reninangiotensin cascade, and sodium handling network may explain the association between FGF1 and BP.
Runs of Homozygosity : Association with Coronary Artery Disease and Gene Expression in Monocytes and Macrophages
- Authors: Christofidou, Paraskevi , Nelson, Christopher , Nikpay, Majid , Qu, Liming , Li, Mingyao , Loley, Christina , Debiec, Radoslaw , Braund, Peter , Denniff, Matthew , Charchar, Fadi , Arjo, Ares Rocanin , Trégouët, David-Alexandre , Goodall, Alison , Cambien, Francois , Ouwehand, Willem , Roberts, Robert , Schunkert, Heribert , Hengstenberg, Christian , Reilly, Muredach , Erdmann, Jeanette , McPherson, Ruth , König, Inke , Thompson, John , Samani, Nilesh , Tomaszewski, Maciej
- Date: 2015
- Type: Text , Journal article
- Relation: American Journal of Human Genetics Vol. 97, no. 2 (2015), p. 228-237
- Full Text: false
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- Description: Runs of homozygosity (ROHs) are recognized signature of recessive inheritance. Contributions of ROHs to the genetic architecture of coronary artery disease and regulation of gene expression in cells relevant to atherosclerosis are not known. Our combined analysis of 24,320 individuals from 11 populations of white European ethnicity showed an association between coronary artery disease and both the count and the size of ROHs. Individuals with coronary artery disease had approximately 0.63 (95% CI: 0.4-0.8) excess of ROHs when compared to coronary-artery-disease-free control subjects (p = 1.49 x 10
Signatures of miR-181a on the renal transcriptome and blood pressure
- Authors: Marques, Francine , Romaine, Simon , Denniff, Matthew , Eales, James , Dormer, John , Garrelds, Ingrid , Wojnar, Lukasz , Musialik, Katarzyna , Duda-Raszewska, Barbara , Kiszka, Bartlomiej , Duda, Magdalena , Morris, Brian , Samani, Nilesh , Jan Danser, Jan , Bogdanski, Pawel , Zukowska-Szczechowska, Ewa , Charchar, Fadi , Tomaszewski, Maciej
- Date: 2015
- Type: Text , Journal article
- Relation: Molecular Medicine Vol. 21, no. (2015), p. 739-748
- Full Text: false
- Reviewed:
- Description: MicroRNA-181a binds to the 3’ untranslated region of messenger RNA (mRNA) for renin, a rate-limiting enzyme of the renin-angiotensin system. Our objective was to determine whether this molecular interaction translates into a clinically meaningful effect on blood pressure and whether circulating miR-181a is a measurable proxy of blood pressure. In 200 human kidneys from the TRANScriptome of renaL humAn TissuE (TRANSLATE) study, renal miR-181a was the sole negative predictor of renin mRNA and a strong correlate of circulating miR-181a. Elevated miR-181a levels correlated positively with systolic and diastolic blood pressure in TRANSLATE, and this association was independent of circulating renin. The association between serum miR-181a and systolic blood pressure was replicated in 199 subjects from the Genetic Regulation of Arterial Pressure of Humans In the Community (GRAPHIC) study. Renal immunohistochemistry and in situ hybridization showed that colocalization of miR-181a and renin was most prominent in collecting ducts where renin is not released into the systemic circulation. Analysis of 69 human kidneys characterized by RNA sequencing revealed that miR-181a was associated with downregulation of four mitochondrial pathways and upregulation of 41 signaling cascades of adaptive immunity and inflammation. We conclude that renal miR-181a has pleiotropic effects on pathways relevant to blood pressure regulation and that circulating levels of miR-181a are both a measurable proxy of renal miR-181a expression and a novel biochemical correlate of blood pressure.
The emerging role of non-coding RNA in essential hypertension and blood pressure regulation
- Authors: Marques, Francine , Booth, Scott , Charchar, Fadi
- Date: 2015
- Type: Text , Journal article
- Relation: Journal of Human Hypertension Vol. 29, no. 8 (2015), p. 459-467
- Relation: http://purl.org/au-research/grants/nhmrc/1009490
- Full Text: false
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- Description: Unravelling the complete genetic predisposition to high blood pressure (BP) has proven to be challenging. This puzzle and the fact that coding regions of the genome account for less than 2% of the entire human DNA support the hypothesis that genetic mechanism besides coding genes are likely to contribute to BP regulation. Non-coding RNAs (ncRNAs) are emerging as key players of transcription regulation in both health and disease states. They control basic functions in virtually all cell types relevant to the cardiovascular system and, thus, a direct involvement with BP regulation is highly probable. Here, we review the literature about ncRNAs associated with human BP and essential hypertension, highlighting investigations, methodology and difficulties arising in the field. The most investigated ncRNAs so far are microRNAs (miRNAs), small ncRNAs that modulate gene expression by posttranscriptional mechanisms. We discuss studies that have examined miRNAs associated with BP in biological fluids, such as blood and urine, and tissues, such as vascular smooth muscle cells and the kidney. Furthermore, we review the interaction between miRNA binding sites and single nucleotide polymorphisms in genes associated with BP. In conclusion, there is a clear need for more human and functional studies to help elucidate the multifaceted roles of ncRNAs, in particular mid- and long ncRNAs in BP regulation. © 2015 Macmillan Publishers Limited All rights reserved.
Acute exercise leads to regulation of Telomere-Associated genes and MicroRNA expression in immune Cells
- Authors: Chilton, Warrick , Marques, Francine , West, Jenny , Kannourakis, George , Berzins, Stuart , O'Brien, Brendan , Charchar, Fadi
- Date: 2014
- Type: Text , Journal article
- Relation: PloS One Vol. 9, no. 4 (2014), p. e92088
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- Description: Telomeres are specialized nucleoprotein structures that protect chromosomal ends from degradation. These structures progressively shorten during cellular division and can signal replicative senescence below a critical length. Telomere length is predominantly maintained by the enzyme telomerase. Significant decreases in telomere length and telomerase activity are associated with a host of chronic diseases; conversely their maintenance underpins the optimal function of the adaptive immune system. Habitual physical activity is associated with longer leukocyte telomere length; however, the precise mechanisms are unclear. Potential hypotheses include regulation of telomeric gene transcription and/or microRNAs (miRNAs). We investigated the acute exercise-induced response of telomeric genes and miRNAs in twenty-two healthy males (mean age = 24.1±1.55 years). Participants undertook 30 minutes of treadmill running at 80% of peak oxygen uptake. Blood samples were taken before exercise, immediately post-exercise and 60 minutes post-exercise. Total RNA from white blood cells was submitted to miRNA arrays and telomere extension mRNA array. Results were individually validated in white blood cells and sorted T cell lymphocyte subsets using quantitative real-time PCR (qPCR). Telomerase reverse transcriptase (TERT) mRNA (P = 0.001) and sirtuin-6 (SIRT6) (P<0.05) mRNA expression were upregulated in white blood cells after exercise. Fifty-six miRNAs were also differentially regulated post-exercise (FDR <0.05). In silico analysis identified four miRNAs (miR-186, miR-181, miR-15a and miR-96) that potentially targeted telomeric gene mRNA. The four miRNAs exhibited significant upregulation 60 minutes post-exercise (P<0.001). Telomeric repeat binding factor 2, interacting protein (TERF2IP) was identified as a potential binding target for miR-186 and miR-96 and demonstrated concomitant downregulation (P<0.01) at the corresponding time point. Intense cardiorespiratory exercise was sufficient to differentially regulate key telomeric genes and miRNAs in white blood cells. These results may provide a mechanistic insight into telomere homeostasis and improved immune function and physical health. Funding NHMRC
Coronary artery disease predisposing haplogroup I of the Y chromosome, aggression and sex steroids - Genetic association analysis
- Authors: Bloomer, Lisa , Nelson, Christopher , Denniff, Matthew , Christofidou, Paraskevi , Debiec, Radoslaw , Thompson, John , Zukowska-Szczechowska, Ewa , Samani, Nilesh , Charchar, Fadi , Tomaszewski, Maciej
- Date: 2014
- Type: Text , Journal article
- Relation: Atherosclerosis Vol. 233, no. 1 (2014), p. 160-164
- Relation: http://purl.org/au-research/grants/nhmrc/1009490
- Full Text: false
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- Description: Objective: Amongst middle-aged men, haplogroup I is associated with approximate to 50% higher risk of coronary artery disease than other paternal lineages of Y chromosome. We hypothesised that carriers of haplogroup I had higher levels of aggression and estrogens and/or lower levels of androgens early in life and thus might be more prone to cardiovascular disease than men with other lineages of Y chromosome. Methods: We reconstructed phylogenetic tree of the Y chromosome in > 1000 young apparently healthy white men from the general population. Each Y chromosome was classified into one of 13 most common European lineages. Androgens (DHEA-S, androstenedione, total testosterone) and their metabolites (total estradiol, estrone) were measured by radioimmunoassays. Information on five dimensions of aggression (total, physical, verbal, anger and hostility) was collected using Buss and Perry questionnaire. Results: Approximately 17% men inherited haplogroup I from their fathers. Carriers of haplogroup I showed lower scores of verbal aggression than men with other haplogroups (beta = -0.72, SE = 0.29, P = 0.012) and when further compared to carriers of most common R1a lineage and other haplogroups (beta = -1.03, SE = 0.34, P = 0.003). However, these associations did not survive a correction for multiple testing. Sex steroids did not show even nominal level of association with haplogroup I. Conclusion: Our data show no overall association between haplogroup I and sex-related phenotypes in young white men. These results also suggest that the previously identified association between haplogroup I and coronary artery disease is not likely mediated by unfavourable profile of sex steroids or heightened aggression early in life. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
Exercise : Putting action into our epigenome
- Authors: Denham, Joshua , Marques, Francine , O'Brien, Brendan , Charchar, Fadi
- Date: 2014
- Type: Text , Journal article
- Relation: Sports Medicine Vol. 44, no. 2 (2014), p. 189-209
- Relation: http://purl.org/au-research/grants/nhmrc/1009490
- Full Text:
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- Description: Most human phenotypes are influenced by a combination of genomic and environmental factors. Engaging in regular physical exercise prevents many chronic diseases, decreases mortality risk and increases longevity. However, the mechanisms involved are poorly understood. The modulating effect of physical (aerobic and resistance) exercise on gene expression has been known for some time now and has provided us with an understanding of the biological responses to physical exercise. Emerging research data suggest that epigenetic modifications are extremely important for both development and disease in humans. In the current review, we summarise findings on the effect of exercise on epigenetic modifications and their effects on gene expression. Current research data suggest epigenetic modifications (DNA methylation and histone acetylation) and microRNAs (miRNAs) are responsive to acute aerobic and resistance exercise in brain, blood, skeletal and cardiac muscle, adipose tissue and even buccal cells. Six months of aerobic exercise alters whole-genome DNA methylation in skeletal muscle and adipose tissue and directly influences lipogenesis. Some miRNAs are related to maximal oxygen consumption (VO 2max) and VO2max trainability, and are differentially expressed amongst individuals with high and low VO2max. Remarkably, miRNA expression profiles discriminate between low and high responders to resistance exercise (miR-378, -26a, -29a and -451) and correlate to gains in lean body mass (miR-378). The emerging field of exercise epigenomics is expected to prosper and additional studies may elucidate the clinical relevance of miRNAs and epigenetic modifications, and delineate mechanisms by which exercise confers a healthier phenotype and improves performance. © 2013 Springer International Publishing Switzerland. Funded by NHMRC; National Health and Medical Research Council
Leukocyte telomere length variation due to DNA extraction method
- Authors: Denham, Joshua , Marques, Francine , Charchar, Fadi
- Date: 2014
- Type: Text , Journal article
- Relation: BMC research notes Vol. 7, no. (2014), p. 877
- Full Text: false
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- Description: Telomere length is indicative of biological age. Shorter telomeres have been associated with several disease and health states. There are inconsistencies throughout the literature amongst relative telomere length measured by quantitative PCR (qPCR) and different extraction methods or kits used. We quantified whole-blood leukocyte telomere length using the telomere to single copy gene (T/S) ratio by qPCR in 20 young (18-25 yrs) men after extracting DNA using three common extraction methods: Lahiri and Nurnberger (high salt) method, PureLink Genomic DNA Mini kit (Life Technologies) and QiaAmp DNA Mini kit (Qiagen). Telomere length differences of DNA extracted from the three extraction methods was assessed by one-way analysis of variance (ANOVA).
Measurement of absolute copy number variation reveals association with essential hypertension
- Authors: Marques, Francine , Prestes, Priscilla , Pinheiro, Leonardo , Scurrah, Katrina , Emslie, Kerry , Tomaszewski, Maciej , Harrap, Stephen , Charchar, Fadi
- Date: 2014
- Type: Text , Journal article
- Relation: BMC Medical Genomics Vol. 7, no. (2014), p. 1-8
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- Description: Background: The role of copy number variation (CNV) has been poorly explored in essential hypertension in part due to technical difficulties in accurately assessing absolute numbers of DNA copies. Droplet digital PCR (ddPCR) provides a powerful new approach to CNV quantitation. The aim of our study was to investigate whether CNVs located in regions previously associated with blood pressure (BP) variation in genome-wide association studies (GWAS) were associated with essential hypertension by the use of ddPCR. Methods: Using a "power of extreme" approach, we quantified nucleic acids using ddPCR in white subjects from the Victorian Family Heart Study with extremely high (n = 96) and low (n = 92) SBP, providing power equivalent to 1714 subjects selected at random. Results: A deletion of the CNVs esv27061 and esv2757747 on chromosome 1p13.2 was significantly more prevalent in extreme high BP subjects after adjustment for age, body mass index and sex (12.6% vs. 2.2%; P = 0.013). Conclusions: Our data suggests that CNVs within regions identified in previous GWAS may play a role in human essential hypertension.
Report of the 3rd annual International Society of Hypertension New Investigator Symposium.
- Authors: Burger, Dylan , Veerabhadrappa, Praveen , Charchar, Fadi , Schutte, Aletta , Tomaszewski, Maciej
- Date: 2014
- Type: Text , Journal article
- Relation: Journal of hypertension Vol. 32, no. 4 (2014), p. 448-449
- Full Text: false
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Small molecules, big effects: The role of microRNAs in regulation of cardiomyocyte death
- Authors: Skommer, Joanna , Rana, Indrajeetsinh , Marques, Francine , Zhu, Wenliang , Du, Zhimin , Charchar, Fadi
- Date: 2014
- Type: Text , Journal article
- Relation: Cell Death and Disease Vol. 5, no. 7 (2014), p. e1325
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- Description: MicroRNAs (miRNAs) are a class of small non-coding RNAs involved in posttranscriptional regulation of gene expression, and exerting regulatory roles in plethora of biological processes. In recent years, miRNAs have received increased attention for their crucial role in health and disease, including in cardiovascular disease. This review summarizes the role of miRNAs in regulation of cardiac cell death/cell survival pathways, including apoptosis, autophagy and necrosis. It is envisaged that these miRNAs may explain the mechanisms behind the pathogenesis of many cardiac diseases, and, most importantly, may provide new avenues for therapeutic intervention that will limit cardiomyocyte cell death before it irreversibly affects cardiac function. Through an indepth literature analysis coupled with integrative bioinformatics (pathway and synergy analysis), we dissect here the landscape of complex relationships between the apoptosis-regulating miRNAs in the context of cardiomyocyte cell death (including regulation of autophagy-apoptosis cross talk), and examine the gaps in our current understanding that will guide future investigations.
- Description: C1
A novel interaction between sympathetic overactivity and aberrant regulation of renin by miR-181a in BPH/2J genetically hypertensive mice
- Authors: Jackson, Kristy , Marques, Francine , Watson, Anna , Palma-Rigo, Keisia , Nguyen-Huu, Thu-Phuc , Morris, Brian , Charchar, Fadi , Davern, Pamela , Head, Geoffrey
- Date: 2013
- Type: Text , Journal article
- Relation: Hypertension Vol. 62 , no. 4 (2013), p. 775-781
- Full Text: false
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- Description: Genetically hypertensive mice (BPH/2J) are hypertensive because of an exaggerated contribution of the sympathetic nervous system to blood pressure. We hypothesize that an additional contribution to elevated blood pressure is via sympathetically mediated activation of the intrarenal renin-angiotensin system. Our aim was to determine the contribution of the renin-angiotensin system and sympathetic nervous system to hypertension in BPH/2J mice. BPH/2J and normotensive BPN/3J mice were preimplanted with radiotelemetry devices to measure blood pressure. Depressor responses to ganglion blocker pentolinium (5 mg/kg i.p.) in mice pretreated with the angiotensin-converting enzyme inhibitor enalaprilat (1.5 mg/kg i.p.) revealed a 2-fold greater sympathetic contribution to blood pressure in BPH/2J mice during the active and inactive period. However, the depressor response to enalaprilat was 4-fold greater in BPH/2J compared with BPN/3J mice, but only during the active period (P=0.01). This was associated with 1.6-fold higher renal renin messenger RNA (mRNA; P=0.02) and 0.8-fold lower abundance of micro-RNA-181a (P=0.03), identified previously as regulating human renin mRNA. Renin mRNA levels correlated positively with depressor responses to pentolinium (r=0.99; P=0.001), and BPH/2J mice had greater renal sympathetic innervation density as identified by tyrosine hydroxylase staining of cortical tubules. Although there is a major sympathetic contribution to hypertension in BPH/2J mice, the renin-angiotensin system also contributes, doing so to a greater extent during the active period and less during the inactive period. This is the opposite of the normal renin-angiotensin system circadian pattern. We suggest that renal hyperinnervation and enhanced sympathetically induced renin synthesis mediated by lower micro-RNA-181a contributes to hypertension in BPH/2J mice.
Consumption of a low glycaemic index diet in late life extends lifespan of Nalb/c mice with differential effects on DNA damage
- Authors: Nankervis, Scott , Mitchell, Jenée , Charchar, Fadi , McGlynn, Maree , Lewandowski, Paul
- Date: 2013
- Type: Text , Journal article
- Relation: Longevity & Healthspan. 2(4) p. 1-13
- Full Text:
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- Description: Background Caloric restriction is known to extend the lifespan of all organisms in which it has been tested. Consequently, current research is investigating the role of various foods to improve health and lifespan. The role of various diets has received less attention however, and in some cases may have more capacity to improve health and longevity than specific foods alone. We examined the benefits to longevity of a low glycaemic index (GI) diet in aged Balb/c mice and examined markers of oxidative stress and subsequent effects on telomere dynamics. Results In an aged population of mice, a low GI diet extended average lifespan by 12%, improved glucose tolerance and had impressive effects on amelioration of oxidative damage to DNA in white blood cells. Telomere length in quadriceps muscle showed no improvement in the dieted group, nor was telomerase reactivated. Conclusion The beneficial effects of a low GI diet are evident from the current study and although the impact to telomere dynamics late in life is minimal, we expect that earlier intervention with a low GI diet would provide significant improvement in health and longevity with associated effects to telomere homeostasis.
Early treatment to prevent hypertension: A laudable goal
- Authors: Harrap, Stephen , Charchar, Fadi
- Date: 2013
- Type: Text , Journal article
- Relation: American Journal of Hypertension Vol. 26, no. 11 (December 2013 2013), p. 1367-1368
- Full Text: false
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Genetic mechanisms of vascular and renal damage
- Authors: Marques, Francine , Tomaszewski, Maciej , Charchar, Fadi
- Date: 2013
- Type: Text , Journal article
- Relation: Journal of Hypertension Vol. 31, no. 11 (2013), p. 2128-2129
- Full Text: false
- Reviewed:
- Description: Document type (note)
- Description: C4
Leading the change: Second International Society of Hypertension New Investigators' Symposium
- Authors: Veerabhadrappa, Praveen , Charchar, Fadi , Burger, Dylan , Tomaszewski, Maciej , Carlberg, Bo
- Date: 2013
- Type: Text , Journal article
- Relation: Journal of Hypertension Vol. 31, no. 2 (February 2013), p. 429-430
- Full Text: false
- Reviewed:
Longer leukocyte telomeres are associated with ultra-endurance exercise independent of cardiovascular risk factors
- Authors: Denham, Joshua , Nelson, Christopher , O'Brien, Brendan , Nankervis, Scott , Denniff, Matthew , Harvey, Jack , Marques, Francine , Codd, Veryan , Zukowska-Szczechowska, Ewa , Samani, Nilesh , Tomaszewski, Maciej , Charchar, Fadi
- Date: 2013
- Type: Text , Journal article
- Relation: PLoS ONE Vol. 8, no. 7 (2013), p.
- Full Text:
- Reviewed:
- Description: Telomere length is recognized as a marker of biological age, and shorter mean leukocyte telomere length is associated with increased risk of cardiovascular disease. It is unclear whether repeated exposure to ultra-endurance aerobic exercise is beneficial or detrimental in the long-term and whether it attenuates biological aging. We quantified 67 ultra-marathon runners' and 56 apparently healthy males' leukocyte telomere length (T/S ratio) using real-time quantitative PCR. The ultra-marathon runners had 11% longer telomeres (T/S ratio) than controls (ultra-marathon runners: T/S ratio = 3.5±0.68, controls: T/S ratio = 3.1±0.41;
- Description: 2003011219
Male-specific region of the y chromosome and cardiovascular risk phylogenetic analysis and gene expression studies
- Authors: Bloomer, Lisa , Nelson, Christopher , Eales, James , Denniff, Matthew , Christofidou, Paraskevi , Debiec, Radoslaw , Moore, Jasbir , Consortium, Cardiogenics , Zukowska-Szczechowska, Ewa , Goodall, Alison , Thompson, John , Samani, Nilesh , Charchar, Fadi , Tomaszewski, Maciej
- Date: 2013
- Type: Text , Journal article
- Relation: Arteriosclerosis, Thrombosis, and Vascular Biology Vol. 33, no. 7 (2013), p. 1722-1727
- Relation: http://purl.org/au-research/grants/nhmrc/1009490
- Full Text:
- Reviewed:
- Description: Objective-Haplogroup I of male-specific region of the human Y chromosome is associated with 50% increased risk of coronary artery disease. It is not clear to what extent conventional cardiovascular risk factors and genes of the malespecific region may explain this association. Approach and Results-A total of 1988 biologically unrelated men from 4 white European populations were genotyped using 11 Y chromosome single nucleotide polymorphisms and classified into 13 most common European haplogroups. Approximately 75% to 93% of the haplotypic variation of the Y chromosome in all cohorts was attributable to I, R1a, and R1b1b2 lineages. None of traditional cardiovascular risk factors, including body mass index, blood pressures, lipids, glucose, C-reactive protein, creatinine, and insulin resistance, was associated with haplogroup I of the Y chromosome in the joint inverse variance meta-analysis. Fourteen of 15 ubiquitous single-copy genes of the male-specific region were expressed in human macrophages. When compared with men with other haplogroups, carriers of haplogroup I had 0.61- and 0.64-fold lower expression of ubiquitously transcribed tetratricopeptide repeat, Y-linked gene (UTY) and protein kinase, Y-linked, pseudogene (PRKY) in macrophages (P=0.0001 and P=0.002, respectively). Conclusions-Coronary artery disease predisposing haplogroup I of the Y chromosome is associated with downregulation of UTY and PRKY genes in macrophages but not with conventional cardiovascular risk factors. © 2013 American Heart Association, Inc.
- Description: 2003011132
RNA sequencing data from the human kidney
- Authors: Charchar, Fadi
- Date: 2013
- Type: Text , Dataset
- Full Text: false
- Description: The aims of the project to determine the molecular cause of human hypertension. We will be studying abnormalities in the expression of RNA in human kidneys. RNA is the message by which DNA or our genes are expressed as protein that makes up most of the cell and its function. The data will consist of RNA sequences and saved as .txt .seq files using the Partek software. The collection contains a sample of 30 items. The data has been processed using sequencing software and collected by the http://www.agrf.org.au Australian Genome Research Facility http://www.agrf.org.au and is funded by a NHMRC project called the effect of non-coding RNA in human hypertension.
Salt Loading in Canola Oil Fed SHRSP Rats Induces Endothelial Dysfunction
- Authors: Papazzo, Annateresa , Conlan, Xavier , Lexis, Louise , Charchar, Fadi , Lewandowski, Paul
- Date: 2013
- Type: Text , Journal article
- Relation: PLoS ONE Vol. 8, no. 6 (2013), p.
- Full Text:
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- Description: This study aimed to determine if 50 days of canola oil intake in the absence or presence of salt loading affects: (1) antioxidant and oxidative stress markers, (2) aortic mRNA of NADPH oxidase (NOX) subunits and superoxide dismutase (SOD) isoforms and (3) endothelial function in SHRSP rats. SHRSP rats were fed a diet containing 10 wt/wt% soybean oil or 10 wt/wt% canola oil, and given tap water or water containing 1% NaCl for 50 days. Without salt, canola oil significantly increased RBC SOD, plasma cholesterol and triglycerides, aortic p22phox, NOX2 and CuZn-SOD mRNA, and decreased RBC glutathione peroxidase activity. With salt, canola oil reduced RBC SOD and catalase activity, LDL-C, and p22phox mRNA compared with canola oil alone, whereas plasma malondialdehyde (MDA) was reduced and RBC MDA and LDL-C were higher. With salt, the canola oil group had significantly reduced endothelium-dependent vasodilating responses to ACh and contractile responses to norepinephrine compared with the canola oil group without salt and to the WKY rats. These results indicate that ingestion of canola oil increases O2 - generation, and that canola oil ingestion in combination with salt leads to endothelial dysfunction in the SHRSP model. © 2013 Papazzo et al.
- Description: 2003011096