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

BMC Cardiovascular Disorders

Research Article

Ailan Chen¹  Yuechun Shen¹  Wenjun Dai²  Caiwen Ou³  Minsheng Chen³  Wanglin Li⁴  Xinyu Chen⁵  Qi Dong⁶  Xinchun Li⁷ 

[1] Department of Cardiology, The First Affiliated Hospital of Guangzhou Medical University, 510120, Guangzhou, China;Department of Cardiology, The Third Affiliated Hospital of Guangzhou Medical University, 510150, Guangzhou, China;Department of Cardiology, Zhujiang Hospital of Southern Medical University, 510280, Guangzhou, China;Department of Gastrointestinal Surgery, Affiliated Guangzhou First Municipal People’s Hospital, Guangzhou Medical University, 51018, Guangzhou, China;Department of Pathogenic Biology, Guangzhou Hoffmann Institute of Immunology, Guangzhou Medical University, 511436, Guangzhou, China;Department of Physiology, Department of Medical Experimental Center, Guangzhou Medical University, 510182, Guangzhou, China;Department of Radiology, The First Affiliated Hospital of Guangzhou Medical University, 510120, Guangzhou, China;

关键词: Metabolic remodeling;    Trimetazidine;    Ventricular hypertrophy;    Neuropeptide Y;   

DOI  :  10.1186/s12872-016-0399-8

 received in 2016-05-27, accepted in 2016-11-08,  发布年份 2016

来源: Springer

【 摘 要 】

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.

【 授权许可】

CC BY   
© The Author(s). 2016