Intravenous (-)-epicatechin reduces myocardial ischemic injury by protecting mitochondrial function

Katrina Go Yamazaki, Aleksander Y. Andreyev, Pilar Ortiz-Vilchis, Susanna Petrosyan, Ajit S. Divakaruni, Sandra E. Wiley, Christine De La Fuente, Guy Perkins, Guillermo Ceballos, Francisco Villarreal, Anne N. Murphy

Research output: Contribution to journalArticlepeer-review

44 Scopus citations

Abstract

Background Targeting the mitochondria during ischemia/reperfusion (IR) can confer cardioprotection leading to improved clinical outcomes. The cardioprotective potential of (-)-epicatechin (EPI) during IR via modulation of mitochondrial function was evaluated. Methods and results Ischemia was induced in rats via a 45 min occlusion of the left anterior descending coronary artery followed by 1 h, 48 h, or 3 week reperfusion. EPI (10 mg/kg) was administered IV 15 min prior to reperfusion for the single dose group and again 12 h later for the double dose group. Controls received water. Experiments also utilized cultured neonatal rat ventricular myocytes (NRVM) and myoblasts. A single dose of EPI reduced infarct size by 27% at 48 h and 28% at 3 week. Double dose treatment further decreased infarct size by 80% at 48 h, and 52% by 3 weeks. The protective effect of EPI on mitochondrial function was evident after 1 h of reperfusion when mitochondria demonstrated less respiratory inhibition, lower mitochondrial Ca2 + load, and a preserved pool of NADH that correlated with higher tissue ATP levels. Mechanistic studies in NRVM revealed that EPI acutely stimulated maximal rates of respiration, an effect that was blocked by inhibitors of the mitochondrial pyruvate carrier, nitric oxide synthase, or soluble guanylyl cyclase. In myoblasts, knockdown of components of the mitochondrial pyruvate carrier blocked EPI-induced respiratory stimulation. Conclusions IV EPI confers cardioprotection via preservation of mitochondrial function potentially through enhanced substrate provision. These provocative results document a novel mechanism of a natural product with potential clinical utility.

Original languageEnglish
Pages (from-to)297-306
Number of pages10
JournalInternational Journal of Cardiology
Volume175
Issue number2
DOIs
StatePublished - 1 Aug 2014

Keywords

  • Cardiac metabolism
  • Epicatechin
  • Mitochondrial pyruvate carrier
  • Myocardial ischemia-reperfusion injury

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