Back to Search
Start Over
Valsartan Promoting Atherosclerotic Plaque Stabilization by Upregulating Renalase
- Source :
- Journal of Cardiovascular Pharmacology and Therapeutics. 20:509-519
- Publication Year :
- 2015
- Publisher :
- SAGE Publications, 2015.
-
Abstract
- Background: Renalase is a protein that can regulate sympathetic nerve activity by metabolizing catecholamines, while redundant catecholamines are thought to contribute to atherosclerosis (As). Catecholamine release can be facilitated by angiotensin (Ang) II by binding to Ang II type 1 (AT1) receptors. Valsartan, a special AT1 antagonist, can dilate blood vessels and reduce blood pressure, but it remained unclear whether valsartan can promote the stability of atherosclerotic plaque by affecting renalase. Objective: This study examined the tissue distribution of renalase in ApoE−/− mice fed with a high-fat diet and the effect of valsartan on expression of renalase. Methods: ApoE−/− mice were fed with a high-fat diet for 13 or 26 weeks. As a control, 10 C57BL mice were fed with a standard chow diet. After 13 weeks on the high-fat diet, the ApoE−/− mice were randomized (10 mice/group) and treated with valsartan, simvastatin, or distilled water (control group) for an additional 13 weeks accompanied by a high-fat diet. Results: Knockout of ApoE caused a dramatic increase in expression of renalase in mice adipose tissue. With the disturbance of lipid metabolism induced by a high-fat diet, renalase expression decreased in the liver. Renalase can be expressed in smooth muscle cells and M2 macrophages in atherosclerotic plaque, and its expression gradually decreases in the fibrous cap during the transition from stable to vulnerable atherosclerotic plaque. Valsartan, an AT1 receptor antagonist, promotes the stabilization of atherosclerotic plaque by increasing the levels of renalase in serum and the expression of renalase in the fibrous cap of atherosclerotic plaque. It also reduces triglyceride levels in serum and increases the expression of renalase in the liver. Conclusions: Renalase may be a potential-related gene of lipid metabolism and As, and it may be the possible molecular target of valsartan to help stabilize atherosclerotic plaque.
- Subjects :
- Male
medicine.medical_specialty
Diet, High-Fat
Real-Time Polymerase Chain Reaction
Mice
Random Allocation
Apolipoproteins E
Internal medicine
medicine
Animals
Pharmacology (medical)
Related gene
Monoamine Oxidase
Renalase
Pharmacology
Analysis of Variance
business.industry
Sympathetic nerve activity
A protein
Lipid metabolism
Lipid Metabolism
Lipids
Angiotensin II
Plaque, Atherosclerotic
Mice, Inbred C57BL
Endocrinology
Valsartan
Cardiology and Cardiovascular Medicine
business
Angiotensin II Type 1 Receptor Blockers
medicine.drug
Subjects
Details
- ISSN :
- 19404034 and 10742484
- Volume :
- 20
- Database :
- OpenAIRE
- Journal :
- Journal of Cardiovascular Pharmacology and Therapeutics
- Accession number :
- edsair.doi.dedup.....5f5aa66579c2b6f49c0e2aa93de87c94