Grape Seed Proanthocyanidin Extract Ameliorates Cardiac Remodelling After Myocardial Infarction Through PI3K/AKT Pathway in Mice.

Lianpin Wu,Yongxue Ruan,Jingguo Wu,Zuoyi Xie,Qike Jin,Kangting Ji,Jingjing Zeng,Lei Li,Fangfang Ren

doi:10.3389/fphar.2020.585984

Abstract

Myocardial infarction is one of the most serious fatal diseases in the world, which is due to acute occlusion of coronary arteries. Grape seed proanthocyanidin extract (GSPE) is an active compound extracted from grape seeds that has anti-oxidative, anti-inflammatory and anti-tumor pharmacological effects. Natural products are cheap, easy to obtain, widely used and effective. It has been used to treat numerous diseases, such as cancer, brain injury and diabetes complications. However, there are limited studies on its role and associated mechanisms in myocardial infarction in mice. This study showed that GSPE treatment in mice significantly reduced cardiac dysfunction and improved the pathological changes due to MI injury. In vitro, GSPE inhibited the apoptosis of H9C2 cells after hypoxia culture, resulting in the expression of Bax decreased and the expression of Bcl-2 increased. The high expression of p-PI3K and p-AKT was detected in MI model in vivo and in vitro. The use of the specific PI3K/AKT pathway inhibitor LY294002 regressed the cardio-protection of GSPE. Our results showed that GSPE could improve the cardiac dysfunction and remodeling induced by MI and inhibit cardiomyocytes apoptosis in hypoxic conditions through the PI3K/AKT signaling pathway.

Highlights

Myocardial infarction (MI) is defined as myocardial cell death caused by long-term ischemia (Jennings and Ganote, 1974)
We studied the effects of Grape seed proanthocyanidin extract (GSPE) on cardiac function and myocardial pathology in mice with MI, as well as the effects of GSPE on the apoptosis of H9C2 cells in a hypoxic environment
triphenyltetrazolium chloride solution (TTC) staining showed that the infarct size of the GSPE group was significantly smaller than that of the MI group (Figure 2A)

Summary

Introduction

Myocardial infarction (MI) is defined as myocardial cell death caused by long-term ischemia (Jennings and Ganote, 1974). In medicine, the clinical definition of MI refers to the detection of abnormal cardiac biomarkers in the presence of acute myocardial ischemia (Thygesen et al, 2018). Previous studies have shown that myocardial injury, defined by an elevated cardiac troponin value, is frequently encountered clinically and is associated with an adverse prognosis (Sarkisian et al, 2016; Sarkisian et al, 2016). Acute MI is the most serious manifestation of coronary artery disease, causing >4 million deaths in North Asia and Europe (Nichols et al, 2014), and >1/3 of all deaths in developed countries every year (Yeh et al, 2010). MI has a great impact on people’s health all over the world, affecting >7 million people every year (Reed et al, 2017)

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