Abstract 122: Angiotensin 1-7 Treatment Improves Cardiac Remodeling in the Heart with Ischemia-Reperfusion
Background: Tissue renin-angiotensin system (RAS) is activated in the injured heart irrespective of the etiologic basis. Angiotensin II (AngII) is well known to promote myocardial remodeling by stimulating inflammation, fibrogenesis and apoptosis. Recently, the classical view of RAS has been challenged by the discovery of the enzyme: angiotensin converting enzyme (ACE)2. The major role for ACE2 is to cleave AngII to generate Ang(1-7). It has been shown that Ang(1-7) counter-balances the cellular actions of AngII. Herein, we sought to determine whether Ang(1-7) is cardiac protective by suppressing myocardial remodeling following ischemia-reperfusion (IR).
Methods and Results: Eight week-old male Sprague Dawley rats were subjected to 10 min of coronary occlusion followed by reperfusion. Rats were infused with Ang(1-7) (1mg/kg/d) or saline by osmotic minipump for 7 days. Untreated sham-operated rats served as controls (n=9/group). The expressions of cardiac RAS, inflammation, fibrosis and apoptosis-related genes at the site of IR damage were detected by RT-PCR. Following IR, cardiac renin, ACE and AT1 receptor mRNA levels were significantly elevated. Compared to sham-operated controls, cardiac gene expressions of NADPH oxidase, ICAM-1, MCP-1, and TNF-alpha (markers of inflammation); TGF-beta, type I and III collagen (markers of fibrogenesis); p53 and caspase-3 (markers of apoptosis) were significantly (p<0.05) increased in rats with IR. Compared to untreated rats with IR, Ang(1-7) treatment significantly suppressed renin and AT1 receptor mRNAs at the site of IR injury. Ang(1-7) treatment also significantly reduced the expression of these inflammation, fibrogenesis and apoptosis-related genes.
Conclusions: Our study has indicated that Ang(1-7) treatment suppresses the inflammatory/fibrogenic response and apoptosis in the heart with IR, which is beneficial to the cardiac remodeling.
- © 2011 by American Heart Association, Inc.