Alteration of Mevalonate Pathway Related Enzyme Expressions in Pressure Overload-Induced Cardiac Hypertrophy and Associated Heart Failure with Preserved Ejection Fraction

Cellular Physiology and Biochemistry

关键词: Mevalonate pathway;    Small GTP-binding proteins;    Pressure overload;    Cardiac hypertrophy;    Diastolic dysfunction;   

DOI  :  10.1159/000356610

学科分类：分子生物学，细胞生物学和基因

来源: S Karger AG

【 摘 要 】

Background Abnormalities of the mevalonate pathway, an important cellular metabolic pathway, are common in many diseases including cardiovascular disease. The mevalonate pathway related enzyme expressions in pressure overload-induced cardiac hypertrophy and associated diastolic dysfunction remains largely unknown. This study aims to investigate whether the expression of mevalonate pathway related enzyme is altered during the progression of cardiac hypertrophy and associated diastolic dysfunction induced by pressure overload. Methods Male Sprague-Dawley (SD) rats were randomly divided into two groups the suprarenal abdominal aortic coarctation (AAC) group and the sham group. Results Histological and echocardiographic assessments showed that there was a significant cardiovascular remodeling in the AAC group compared with the sham group after 3 weeks post-operatively, and the left ventricular (LV) diastolic function was reduced at 8 and 14 weeks post-operatively in the AAC group, without any change in systolic function during the study. The tissue of the heart and the abdominal aorta proximal to the coarctation showed over-expression of several enzymes, including 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR), farnesyl diphosphate synthase (FDPS), farnesyltransferase-α (FNTA), farnesyltransferase-β (FNTB), geranylgeranyltransferase type I (GGTase-I) and the activation of their downstream proteins was enhanced. Conclusions AAC induced compensatory LV hypertrophy to decompensatory diastolic dysfunction, accompanied by altered expression of several key enzymes in the mevalonate pathway.

【 授权许可】

CC BY-NC-ND