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Jawahar L. Mehta, M.D., Ph.D., University of Arkansas for Medical Sciences and CAVHS, Little Rock, AR, USA
Inflammation is present in the heart soon after acute myocardial infarction and continues during the chronic stage. Autophagy is a physiologic process for tissue survival. We hypothesized that inflammation may promote cardiomyocyte autophagy and protect cardiomyocytes from death during the ischemic process. To address this hypothesis, we used the myocardial infract mouse model (total left coronary artery occlusion) to investigate the relationship between inflammation and autophagy at different time points after. Our data showed that inflammation (TNF-a and IL-6) and autophagic (LC-3 and Beclin-1) responses were strongest during the first week, and then declined over the next 3 weeks. The maximal increase in inflammation and autophagy was in the border zone. To elucidate the role of inflammation in cardiomyocyte autophagy and its impact on cardiac function, we treated mice with TNF-a inhibitor during the first week after total left coronary artery occlusion, and measured infarct size, cytokine release and autophagy. We observed that anti-TNF-a treatment markedly reduced leukocyte infiltration and pro-inflammatory cytokine levels in the heart and sera (all P<0.05). The infarct size was somewhat increased, and autophagy signals were diminished compared to controls (P<0.01). Most importantly, cardiac function measured by echocardiography (FS and EF) was modestly but significantly (P<0.05) decreased. Our findings indicate that inflammatory responses may be protective in the early stage of myocardial infarction by stimulation of cardiomyocyte autophagy, and anti-inflammatory therapy at this stage may be harmful.
