Background
There is evidence for inflammation, autophagy, and apoptosis in the ischemic heart. Autophagy is a physiologic process for tissue survival. Apoptosis, on the other hand, is a mechanism that serves to clear the debris in the setting of tissue injury. The balance between autophagy and apoptosis may be important in cell survival and cardiac function.
Conclusions
These observations suggest that inflammatory response may be protective in the early stage of the myocardial infarction through stimulation of myocyte autophagy. Anti-inflammatory treatment early after coronary occlusion may have an adverse effect.
Results
We examined the interplay of inflammation and myocyte autophagy and apoptosis during the ischemic process. We subjected mice to total left coronary artery ligation and studied these animals for up to 4 weeks. The inflammatory (tumor necrosis factor [TNF]-α, monocyte chemoattractant protein-1, interleukin-6, and interleukin-1β) and autophagic signals (light chain-3 and beclin-1) were strongest during the first week and then began to decline. However, the apoptotic signals peaked at week 2 after left coronary artery ligation, and the elevated levels persisted until the end of the fourth week. To elucidate the role of inflammation in the regulation of myocyte autophagy and apoptosis, we administered TNF-α inhibitor (CAS1049741-03-8, Millipore, Burlington, MA) to the mice daily during the first week of myocardial infarction. Anti-TNF-α therapy reduced the levels of inflammatory cytokines and the inflammatory cell infiltration in and around the infarct area. However, cardiac function measured by echocardiography (fractional shortening and ejection fraction) worsened with anti-TNF-α therapy. More importantly, application of TNF-α inhibitor markedly inhibited autophagy and promoted myocyte apoptosis in the border zone. Conclusions: These observations suggest that inflammatory response may be protective in the early stage of the myocardial infarction through stimulation of myocyte autophagy. Anti-inflammatory treatment early after coronary occlusion may have an adverse effect.