期刊
CIRCULATION-HEART FAILURE
卷 2, 期 4, 页码 342-350出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/CIRCHEARTFAILURE.108.812099
关键词
angiotensin II; endothelin-1; mitochondrial biogenesis; heart failure; proliferator-activated receptor-gamma; coactivator-1 alpha
资金
- European Union [2005-018833/EUGeneHeart]
Background-Evidence is emerging to support the concept that the failing heart is energy depleted and that defects in energy metabolism are important determinants in the development and the progression of the disease. We have shown previously that depressed mitochondrial function in cardiac and skeletal muscles in chronic heart failure is linked to decreased expression of the gene encoding transcriptional proliferator-activated receptor-gamma coactivator-1 alpha, the inducible regulator of mitochondrial biogenesis and its transcription cascade, leading to altered expression of mitochondrial proteins. However, oxidative capacity of the myocardium of patients treated for chronic heart failure and pathophysiological mechanisms of mitochondrial dysfunction are still largely unknown. Methods and Results-In patients with chronic heart failure treated with angiotensin-converting enzyme inhibition, cardiac oxidative capacity, measured in saponin-permeabilized fibers, was 25% lower, and proliferator-activated receptor-gamma coactivator-1 alpha protein content was 34% lower compared with nonfailing controls. In a rat model of myocardial infarction, angiotensin-converting enzyme inhibition therapy was only partially able to protect cardiac mitochondrial function and transcription cascade. Expression of proliferator-activated receptor-gamma coactivator-1 alpha and its transcription cascade were evaluated after a 48-hour exposure of cultured adult rat ventricular myocytes to endothelin-1, angiotensin II, aldosterone, phenylephrine, or isoprenaline. Endothelin-1 (-30%) and, to a lesser degree, angiotensin II (-20%) decreased proliferator-activated receptor-gamma coactivator-1 alpha mRNA content, whereas other hormones had no effect (phenylephrine) or even increased it (aldosterone, isoprenaline). Conclusions-Taken together, these results show that, despite angiotensin-converting enzyme inhibition treatment, oxidative capacity is reduced in human and experimental heart failure and that endothelin-1 and angiotensin II could be involved in the downregulation of the mitochondrial transcription cascade. (Circ Heart Fail. 2009;2:342-350.)
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据