Trimetazidine attenuates pressure overload-induced early cardiac energy dysfunction via regulation of neuropeptide Y system in a rat model of abdominal aortic constriction.

Ailan Chen,Wanglin Li,Xinchun Li,Xinyu Chen,Qi Dong,Minsheng Chen,Wenjun Dai,Caiwen Ou,Yuechun Shen

doi:10.1186/s12872-016-0399-8

Abstract

BackgroundMetabolism remodeling has been recognized as an early event following cardiac pressure overload. However, its temporal association with ventricular hypertrophy has not been confirmed. Moreover, whether trimetazidine could favorably affect this process also needs to be determined. The aim of the study was to explore the temporal changes of myocardial metabolism remodeling following pressure-overload induced ventricular hypertrophy and the potential favorable effect of trimetazidine on myocardial metabolism remodeling.MethodsA rat model of abdominal aortic constriction (AAC)-induced cardiac pressure overload was induced. These rats were grouped as the AAC (no treatment) or TMZ group according to whether oral trimetazidine (TMZ, 40 mg/kg/d, for 5 days) was administered. Changes in cardiac structures were sequentially evaluated via echocardiography. The myocardial ADP/ATP ratio was determined to reflect the metabolic status, and changes in serum neuropeptide Y systems were evaluated.ResultsMyocardial metabolic disorder was acutely induced as evidenced by an increased ADP/ATP ratio within 7 days of AAC before the morphological changes in the myocardium, accompanied by up-regulation of serum oxidative stress markers and expression of fetal genes related to hypertrophy. Moreover, the serum NPY and myocardial NPY-1R, 2R, and 5R levels were increased within the acute phase of AAC-induced cardiac pressure overload. Pretreatment with TMZ could partly attenuate myocardial energy metabolic homeostasis, decrease serum levels of oxidative stress markers, attenuate the induction of hypertrophy-related myocardial fetal genes, inhibit the up-regulation of serum NPY levels, and further increase the myocardial expression of NPY receptors.ConclusionsCardiac metabolic remodeling is an early change in the myocardium before the presence of typical morphological ventricular remodeling following cardiac pressure overload, and pretreatment with TMZ may at least partly reverse the acute metabolic disturbance, perhaps via regulation of the NPY system.

Highlights

Metabolism remodeling has been recognized as an early event following cardiac pressure overload
Effects of TMZ on left ventricular hypertrophy and cardiac function in abdominal aortic constriction (AAC) rats To observe the acute impact of pressure overload on cardiac hypertrophy and cardiac function, we measured the dimensions of the left ventricle and cardiac systolic function via echocardiography
The results of the echocardiographic examination showed that the parameters of left ventricular dimensions, such as interventricular septal thickness at end diastole (IVSd), LVPWd, left ventricular enddiastolic dimension (LVEDD), and left ventricular end-systolic dimension (LVESD), as well as the indices of cardiac systolic function, including left ventricular factional shortening (LVFS) and left ventricular ejection fraction (LVEF), were not significantly different between the rats from the sham and AAC groups at 2 or 7 days after AAC (Table 2)

Summary

Introduction

Metabolism remodeling has been recognized as an early event following cardiac pressure overload. The aim of the study was to explore the temporal changes of myocardial metabolism remodeling following pressure-overload induced ventricular hypertrophy and the potential favorable effect of trimetazidine on myocardial metabolism remodeling. Various stimuli of cardiac injury lead to impairment of cardiac function and subsequently activation of neurohormonal factors, which in the long-term, causes apoptosis of cardiomyocytes, fibrosis and eventually hypertrophy of the myocardium, leading to a vicious cycle of cardiac function deterioration [5] This pathogenetic process has been known as ventricular remodeling, and inhibitors of neurohormonal factors that are involved in the activation of ventricular remodeling have been recognized as important therapeutic medications against CHF [6]. To the best of our knowledge, the acute changes in energy status during the early phase of cardiac pressure overload, a conventional stimulus of cardiac remodeling, have not been systematically studied

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