title: Valsartan Promoting Atherosclerotic Plaque Stabilization by Upregulating Renalase: A Potential-Related Gene of Atherosclerosis.
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.
authors.affiliation: Beijing Hospital of TCM Affiliated with Capital Medical University, Beijing Institute of TCM, Beijing, China Both the authors contributed equally to this work mingxue78@163.com.
authors.forename: Mingxue
authors.initials: M
authors.lastname: Zhou
authors.affiliation: School of Life Science, Tsinghua University, Beijing, China Both the authors contributed equally to this work.
authors.forename: Chao
authors.initials: C
authors.lastname: Ma
authors.affiliation: Beijing Hospital of TCM Affiliated with Capital Medical University, Beijing Institute of TCM, Beijing, China.
authors.forename: Weihong
authors.initials: W
authors.lastname: Liu
authors.affiliation: Beijing Hospital of TCM Affiliated with Capital Medical University, Beijing, China.
authors.forename: Hongxu
authors.initials: H
authors.lastname: Liu
authors.affiliation: Beijing Hospital of TCM Affiliated with Capital Medical University, Beijing Institute of TCM, Beijing, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Wang
authors.affiliation: Beijing Hospital of TCM Affiliated with Capital Medical University, Beijing Institute of TCM, Beijing, China.
authors.forename: Qunfu
authors.initials: Q
authors.lastname: Kang
authors.affiliation: Beijing Hospital of TCM Affiliated with Capital Medical University, Beijing Institute of TCM, Beijing, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Li
mesh_terms: D000704:Analysis of Variance; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics; D059305:Diet, High-Fat; D050356:Lipid Metabolism / Q000187:drug effects* / Q000235:genetics*; D008055:Lipids / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008995:Monoamine Oxidase / Q000235:genetics* / Q000378:metabolism; D058226:Plaque, Atherosclerotic / Q000188:drug therapy*; D011897:Random Allocation; D060888:Real-Time Polymerase Chain Reaction; D000068756:Valsartan / Q000494:pharmacology*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D001057:Apolipoproteins E; D008055:Lipids; D000068756:Valsartan; D008995:Monoamine Oxidase; C521557:renalase
keywords: angiotensin II; atherosclerosis; atherosclerotic plaque stabilization; lipid metabolism; renalase