Moxonidine increases uptake of oxidised low-density lipoprotein in cultured vascular smooth muscle cells and inhibits atherosclerosis in apolipoprotein E-deficient mice
- Wang, Yutang, Nguyen, Dinh, Anesi, Jack, Alramahi, Ahmed, Witting, Paul, Chai, Zhonglin, Khan, Abdul, Kelly, Jason, Denton, Kate, Golledge, Jonathan
- Authors: Wang, Yutang , Nguyen, Dinh , Anesi, Jack , Alramahi, Ahmed , Witting, Paul , Chai, Zhonglin , Khan, Abdul , Kelly, Jason , Denton, Kate , Golledge, Jonathan
- Date: 2023
- Type: Text , Journal article
- Relation: International Journal of Molecular Sciences Vol. 24, no. 4 (2023), p.
- Relation: https://purl.org/au-research/grants/nhmrc/1062671
- Full Text:
- Reviewed:
- Description: This study aimed to investigate the effect of the sympatholytic drug moxonidine on atherosclerosis. The effects of moxonidine on oxidised low-density lipoprotein (LDL) uptake, inflammatory gene expression and cellular migration were investigated in vitro in cultured vascular smooth muscle cells (VSMCs). The effect of moxonidine on atherosclerosis was measured by examining aortic arch Sudan IV staining and quantifying the intima-to-media ratio of the left common carotid artery in apolipoprotein E-deficient (ApoE
- Authors: Wang, Yutang , Nguyen, Dinh , Anesi, Jack , Alramahi, Ahmed , Witting, Paul , Chai, Zhonglin , Khan, Abdul , Kelly, Jason , Denton, Kate , Golledge, Jonathan
- Date: 2023
- Type: Text , Journal article
- Relation: International Journal of Molecular Sciences Vol. 24, no. 4 (2023), p.
- Relation: https://purl.org/au-research/grants/nhmrc/1062671
- Full Text:
- Reviewed:
- Description: This study aimed to investigate the effect of the sympatholytic drug moxonidine on atherosclerosis. The effects of moxonidine on oxidised low-density lipoprotein (LDL) uptake, inflammatory gene expression and cellular migration were investigated in vitro in cultured vascular smooth muscle cells (VSMCs). The effect of moxonidine on atherosclerosis was measured by examining aortic arch Sudan IV staining and quantifying the intima-to-media ratio of the left common carotid artery in apolipoprotein E-deficient (ApoE
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.
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