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Olmesartan prevents cardiac rupture in mice with myocardial infarction by modulating growth differentiation factor 15 and P53.
MedLine Citation:
PMID:  24749959     Owner:  NLM     Status:  Publisher    
BACKGROUND AND PURPOSE: Cardiac rupture is a catastrophic complication after acute myocardial infarction and lacks effective pharmacological prevention. Here we investigated the effect of angiotensin II receptor blocker (ARB) olmesartan (Olm) on post-infarct cardiac rupture and the underlying mechanisms.
EXPERIMENTAL APPROACH: C57Bl/6 mice with myocardial infarction (MI) were treated with Olm or aldosterone (Aldo) or vehicle. Cultured neonatal cardiomyocytes and fibroblasts were exposed to normoxia or anoxia and treated with angiotensin II (Ang II), RNH6270 (active ingredient of Olm), or Aldo.
KEY RESULTS: The mortality rate and incidence of cardiac rupture in MI mice during the 1(st) week in Olm-treated group were significantly lower than in vehicle-treated group. Olm or RNH6270 reduced myeloperoxidase staining in the infarcted myocardium, decreased apoptosis in cultured cardiomyocytes and fibroblasts as assessed by Hoechst staining and TUNEL assay, attenuated the accumulation of p53 and phosphorylated p53 and cleavage caspase 3 induced by MI or Ang II as assessed by western blotting, and upregulated growth differentiation factor-15 (GDF-15). In cultured cardiomyocytes and fibroblasts, treatment with Ang II, Aldo or anoxia significantly down-regulated the expression of GDF-15.
CONCLUSIONS AND IMPLICATIONS: Olm prevents cardiac rupture through inhibition of apoptosis and inflammation, which is attributable to the downregulation of p53 activity and upregulation of GDF-15. Our findings suggest that earlier administration of ARB in patients with AMI is a potential preventive approach for cardiac rupture.
Baihe Chen; Di Lu; Yujuan Fu; Jingwen Zhang; Xiaobo Huang; Shiping Cao; Dingli Xu; Jianping Bin; Masafumi Kitakaze; Qiaobing Huang; Yulin Liao
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-4-18
Journal Detail:
Title:  British journal of pharmacology     Volume:  -     ISSN:  1476-5381     ISO Abbreviation:  Br. J. Pharmacol.     Publication Date:  2014 Apr 
Date Detail:
Created Date:  2014-4-22     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7502536     Medline TA:  Br J Pharmacol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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This article is protected by copyright. All rights reserved.
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