Mitochondrial DNA-induced inflammatory damage contributes to myocardial ischemia reperfusion injury in rats: Cardioprotective role of epigallocatechin

Abstract

Inflammation serves an important role in the pathogenesis of myocardial ischemia/reperfusion (I/R) injury. Fragments of endogenous damaged‑associated molecular patterns, recently identified as mitochondrial DNA (mtDNA), have been proven to be a potent pro‑inflammatory mediator. Epigallocatechin‑3‑gallate (EGCG) is able to regulate the expression levels of a series of inflammatory cytokines. However, the involvement of endogenous mtDNA in EGCG‑regulated inflammatory activities in the context of myocardial I/R injury remains to be elucidated. The present study was designed to investigate the role of mtDNA in EGCG‑mediated myocardial protection in a rat I/R model. Significant positive correlations between elevated plasma mtDNA copy numbers and the expression levels of tumor necrosis factor (TNF) and interleukins (IL)‑6 and ‑8 were observed in the myocardial tissue following an I/R injury (P<0.05). However, EGCG administered prior to reperfusion was able to effectively downregulate the expression levels of plasma mtDNA, TNF and IL‑6 and ‑8 in the myocardial tissue following an I/R injury (P<0.05). Limited infarct size, reduced severity of myocardial injury and decreased incidence of ventricular arrhythmia were observed in the EGCG‑treated group. However, the beneficial effects of EGCG in preventing myocardial I/R injury may be eliminated by a specific phosphoinositide‑3‑kinase (PI3K) inhibitor. These results suggested that EGCG‑mediated cardioprotective effects may be achieved by inhibiting the release of mtDNA from damaged mitochondria and that this protection was at least in part dependent on the PI3K/RAC‑α serine/threonine‑protein kinase associated signaling pathway.