Trimetazidine Protects against Smoking-Induced Left Ventricular Remodeling via Attenuating Oxidative Stress, Apoptosis, and Inflammation

Xiang Zhou,Chao Li,Weiting Xu,Jianchang Chen,Partha Mukhopadhyay

doi:10.1371/journal.pone.0040424

Abstract

Trimetazidine, a piperazine derivative used as an anti-anginal agent, improves myocardial glucose utilization through inhibition of fatty acid metabolism. The present study was designed to investigate whether trimetazidine has the protective effects against smoking-induced left ventricular remodeling in rats. In this study, Wistar rats were randomly divided into 3 groups: smoking group (exposed to cigarette smoke), trimetazidine group (exposed to cigarette smoke and treated with trimetazidine), and control group. The echocardiographic and morphometric data indicated that trimetazidine has protective effects against smoking-induced left ventricular remodeling. Oxidative stress was evaluated by detecting malondialdehyde, superoxide dismutase, and glutathione peroxidase in the supernatant of left ventricular tissue. Cardiomyocyte apoptotic rate was determined by flow cytometry with Annexin V/PI staining. Gene expression and serum levels of inflammatory markers, including interleukin-1β, interleukin-6, and tumor necrosis factor-α, were deteced by quantitative real-time PCR and enzyme-linked immunosorbent assay. Our results suggested that trimetazidine could significantly reduce smoking-induced oxidative stress, apoptosis, and inflammation. In conclusion, our study demonstrates that trimetazidine protects against smoking-induced left ventricular remodeling via attenuating oxidative stress, apoptosis, and inflammation.

Highlights

Smoking, which is a serious public health concern, contributes significantly to cardiovascular morbidity and mortality [1,2,3,4]
Left ventricular mass index (LVMI), cross-sectional area (CSA) and Interstitial collagen volume fraction (ICVF) in the smoking group were significantly higher than in the control group, whereas these three variables were significantly lower in the trimetazidine group compared to the smoking group
We demonstrated for the first time that trimetazidine has protective effects against smoking-induced left ventricular remodeling via attenuating oxidative stress, apoptosis, and inflammation

Summary

Introduction

Smoking, which is a serious public health concern, contributes significantly to cardiovascular morbidity and mortality [1,2,3,4]. Cigarette smoke contains more than 4,000 chemical substances, including polycyclic aromatic hydrocarbons and oxidative gases, most of which exert a cardiotoxic effect. Nicotine is the addictive component and most harmful ingredient contained within cigarettes. We concluded that nicotine promotes cardiomyocyte apoptosis by inducing oxidative stress and disrupting apoptosis-related gene expression [5]. Ventricular remodeling, defined as changes in size, shape and function of the heart in response to cardiac injury or increased load, is associated with the development and progression of heart failure. In the past few years, several studies have demonstrated that exposure to cigarette smoke can result in cardiac remodeling and impaired ventricular function [7,8,9]

Methods

Results

Conclusion