Trimetazidine attenuates pressure overload-induced early cardiac energy dysfunction via regulation of neuropeptide Y system in a rat model of abdominal aortic constriction
Autor: | Wenjun Dai, Ailan Chen, Minsheng Chen, Xinchun Li, Caiwen Ou, Xinyu Chen, Wanglin Li, Qi Dong, Yuechun Shen |
---|---|
Jazyk: | angličtina |
Předmět: |
Male
Receptors Neuropeptide 0301 basic medicine medicine.medical_specialty Ventricular hypertrophy Trimetazidine 030204 cardiovascular system & hematology Ventricular Function Left Receptors G-Protein-Coupled Muscle hypertrophy 03 medical and health sciences Adenosine Triphosphate 0302 clinical medicine Internal medicine medicine Animals Arterial Pressure Neuropeptide Y Aorta Abdominal Rats Wistar Ventricular remodeling Pressure overload Ventricular Remodeling business.industry Myocardium Metabolic disorder Cardiovascular Agents medicine.disease Neuropeptide Y receptor Constriction Receptors Neuropeptide Y Adenosine Diphosphate Disease Models Animal Oxidative Stress 030104 developmental biology Endocrinology Gene Expression Regulation Cardiovascular agent Cardiology Hypertrophy Left Ventricular Metabolic remodeling Energy Metabolism business Cardiology and Cardiovascular Medicine Signal Transduction Research Article medicine.drug |
Zdroj: | BMC Cardiovascular Disorders |
ISSN: | 1471-2261 |
DOI: | 10.1186/s12872-016-0399-8 |
Popis: | Background Metabolism 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. Methods A 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. Results Myocardial 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. Conclusions Cardiac 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. |
Databáze: | OpenAIRE |
Externí odkaz: |