ACE2 activity was increased in atherosclerotic plaque by losartan: Possible relation to anti-atherosclerosis.

Abstract

INTRODUCTION:

Angiotensin-converting enzyme 2 (ACE2) is a new member of the renin-angiotensin system (RAS) and it has been proposed that ACE2 is a potential therapeutic target for the control of cardiovascular disease. The effect of losartan on the ACE2 activity in atherosclerosis was studied.

METHODS:

Atherosclerosis was induced in New Zealand white rabbits by high-cholesterol diet for 3 months. An Angiotensin II (Ang II) receptor blocker (losartan, 25 mg/kg/d) was given for 3 months. ACE2 activity was measured by fluorescence assay and the extent of atherosclerosis was evaluated by H&E and Oil Red O staining. In addition, the effect of losartan on ACE2 activity in smooth muscle cells (SMCs) in vitro was also evaluated.

RESULTS:

Losartan increased ACE2 activity in atherosclerosis in vivo and SMCs in vitro. Losartan inhibited atherosclerotic evolution. Addition of losartan blocked Ang II-induced down-regulation of ACE2 activity, and blockade of extracellular signal-regulated kinase (ERK1/2) with PD98059 prevented Ang II-induced down-regulation of ACE2 activity.

CONCLUSIONS:

The results showed that ACE2 activity was regulated in atherosclerotic plaque by losartan, which may play an important role in treatment of atherosclerosis. The mechanism involves Ang II-AT1R-mediated mitogen-activated protein kinases, MAPKs (MAPKs) signaling pathway.

• Authors: Yue Hui Zhang, Qing Qing Hao, Xiao Yu Wang, Xu Chen, Nan Wang, Li Zhu, Shu Ying Li, Qing Tao Yu, Bo Dong
• Journal: Journal of the renin-angiotensin-aldosterone system : JRAAS (J Renin Angiotensin Aldosterone Syst) Vol. 16 Issue 2 Pg. 292-300 (Jun 2015) ISSN: 1752-8976 [Electronic] England
• PMID: 25070352 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The Author(s) 2014.

Chemical References

• Peptide Fragments
• Angiotensin I
• Extracellular Signal-Regulated MAP Kinases
• Peptidyl-Dipeptidase A
• ACE2 protein, human
• Angiotensin-Converting Enzyme 2
• angiotensin I (1-7)
• Losartan

Topics

• Angiotensin I (metabolism)
• Angiotensin-Converting Enzyme 2
• Animals
• Down-Regulation (drug effects)
• Extracellular Signal-Regulated MAP Kinases (metabolism)
• Humans
• Losartan (pharmacology, therapeutic use)
• Male
• Myocytes, Smooth Muscle (drug effects, metabolism)
• Peptide Fragments (metabolism)
• Peptidyl-Dipeptidase A (metabolism)
• Plaque, Atherosclerotic (drug therapy, enzymology, pathology)
• Rabbits
• Signal Transduction (drug effects)