Effects of (−)-Epicatechin on Myocardial Infarct Size and Left Ventricular Remodeling After Permanent Coronary Occlusion

Abstract

Objectives We examined the effects of the flavanol (−)-epicatechin on short and long-term infarct size and left ventricular (LV) structure/function after permanent coronary occlusion (PCO) and the potential involvement of the protective AKT/ERK signaling pathways. Background (−)-Epicatechin reduces blood pressure in hypertensive patients and limits infarct size in animal models of myocardial ischemia-reperfusion injury. However, nothing is known about its effects on infarction after PCO. Methods (−)-Epicatechin (1mg/kg/day) treatment (Tx) was administered via daily oral gavage to 250 g male rats for 10 days prior to PCO and continued afterwards. PCO controls received water. Sham animals underwent thoracotomy and treatment in the absence of PCO. Immunoblots assessed AKT/ERK involvement 2 h after PCO. LV morphometry and function were measured 48 h and 3 weeks post-PCO. Results In the 48 h group, Tx reduced infarct size by 52%. There were no differences in hemodynamics amongst the different groups (heart rate, aortic and LV pressures). Western blots revealed no differences in AKT or ERK phosphorylation levels. At 3 weeks, PCO control animals demonstrated significant increases in LV end-diastolic pressure, heart weight/body weight, and LV chamber diameter vs. sham. PCO + (−)-epicatechin group values were comparable to sham + (−)-epicatechin. Tx resulted in a 33% decrease in MI size. LV pressure-volume curves demonstrated a right shift in control PCO animals, whereas (−)-epicatechin were comparable to sham. LV scar area strains were significantly improved with (−)-epicatechin. Conclusions These results demonstrate the unique capacity of (−)-epicatechin to confer cardioprotection in the setting of a severe form of myocardial ischemic injury. Protection is sustained over time and preserves LV structure/function. The cardioprotective mechanism(s) of (−)-epicatechin appear unrelated to AKT or ERK activation. (−)-Epicatechin warrants further investigation as a cardioprotectant.

(–)-Epicatechin Suppresses Angiotensin II-induced Cardiac Hypertrophy via the Activation of the SP1/SIRT1 Signaling Pathway

“…It has been reported that EPI can reduce the mortality of CVD [29]. The protective effect of EPI may occur via a reduction in oxidative stress, and improvement of mitochondrial structure and function [15-17]. Previous studies have also revealed that EPI-rich cocoa treatment improved mitochondrial structure and enhanced cardiac and/or SkM muscle function in patients with heart failure [18].…”

“…Epicatechin (EPI) is considered an important factor that may be responsible for the beneficial effects of these flavanol-rich foods [13, 14]. Pharmacological studies have found that EPI exhibits protective effects on oxidative stress injury, myocardial ischemia reperfusion injury and permanent coronary occlusion [15-17]. EPI treatment also improved mitochondrial structure in enhanced cardiac and/or SkM muscle function in patients with heart failure.…”

(−)-Epicatechin induces calcium and translocation independent eNOS activation in arterial endothelial cells

“…It is well accepted that the activation of eNOS can exert cardioprotective effects (32,18) and thus, agents that stimulate its activity may be of therapeutic interest. In support of this, we recently reported on the cardioprotective effects of EPI on animals subjected to ischemiareperfusion or permanent coronary occlusion (35,36).…”

Exercise Pills: At the Starting Line

“…Some animal studies demonstrate that (-)-epicatechin increases NO production in endothelial cells [78] and attenuates myocardial injury [79,80]. There are several studies showing that the NO pathway may play a role in mitochondrial biogenesis [81][82][83] and angiogenesis [84] in skeletal muscle.…”