Myocardial autophagy variation during acute myocardial infarction in rats: The effects of carvedilol

Department of Surgical Intensive Care Unit, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China.
Chinese medical journal (Impact Factor: 1.05). 10/2009; 122(19):2372-9. DOI: 10.3760/cma.j.issn.0366-6999.2009.19.033
Source: PubMed


The loss of cardiac myocytes is one of the mechanisms involved in acute myocardial infarction (AMI)-related heart failure. Autophagy is a common biological process in eukaryote cells. The relationship between cardiac myocyte loss and autophagy after AMI is still unclear. Carvedilol, a non-selective alpha1- and beta-receptor blocker, also suppresses cardiac myocyte necrosis and apoptosis induced by ischemia. However, the association between the therapeutic effects of carvedilol and autophagy is still not well understood. The aim of the present study was to establish a rat model of AMI and observe changes in autophagy in different zones of the myocardium and the effects of carvedilol on autophagy in AMI rats.
The animals were randomly assigned to a sham group, an AMI group, a chloroquine intervention group and a carvedilol group. The AMI rat model was established by ligating the left anterior descending coronary artery. The hearts were harvested at 40 minutes, 2 hours, 24 hours and 2 weeks after ligation in the AMI group, at 40 minutes in the chloroquine intervention group and at 2 weeks in other groups. Presence of autophagic vacuoles (AV) in the myocytes was observed by electron microscopy. The expression of autophagy-, anti-apoptotic- and apoptotic-related proteins, MAPLC-3, Beclin-1, Bcl-xl and Bax, were detected by immunohistochemical staining and Western blotting.
AVs were not observed in necrotic regions of the myocardium 40 minutes after ligation of the coronary artery. A large number of AVs were found in the region bordering the infarction. Compared with the infarction region and the normal region, the formation of AV was significantly increased in the region bordering the infarction (P < 0.05). The expression of autophagy- and anti-apoptotic-related proteins was significantly increased in the region bordering the infarction. Meanwhile, the expression of apoptotic-related proteins was significantly increased in the infarction region. In the chloroquine intervention group, a large number of initiated AVs (AVis) were found in the necrotic myocardial region. At 2 weeks after AMI, AVs were frequently observed in myocardial cells in the AMI group, the carvedilol group and the sham group, and the number of AVs was significantly increased in the carvedilol group compared with both the AMI group and the sham group (P < 0.05). The expression of autophagy- and anti-apoptotic-related proteins was significantly increased in the carvedilol group compared with that in the AMI group, and the positive expression located in the infarction region and the region bordering the infarction.
AMI induces the formation of AV in the myocardium. The expression of anti-apoptosis-related proteins increases in response to upregulation of autophagy. Carvedilol increases the formation of AVs and upregulates autophagy and anti-apoptosis of the cardiac myocytes after AMI.

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    • "The sample volume is 40 μg. Proteins were transferred to a polyvinylidene membrane [31, 32]. Rat anti-Bcl-2 monoclonal antibody (Santa Cruz Biotechnology; Santa Cruz, CA) and mouse anti-Bax monoclonal antibody (Santa Cruz Biotechnology; Santa Cruz, CA) were used for Bcl-2 and Bax detection, respectively. "
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    • "Acute myocardial infarction (AMI) was induced in rats as described previously. In brief, animals were anesthetized by intraperitoneal injection of sodium pentobarbital (50 mg/kg), and AMI was established as described previously [30]. After implanting the electrocardiogram monitor, the rat was connected to a respirator through tracheotomy, and the heart was rapidly exteriorized through left thoracotomy and pericardial incision. "
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