期刊
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
卷 41, 期 3, 页码 459-466出版社
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.yjmcc.2006.06.004
关键词
angiotensin; metabolism; genes; hypertrophy; heart failure
Heart failure is associated with downregulation of the fatty acid oxidation pathway in the ventricular myocardium. Since angiotensin II plays a critical role in myocardial phenotypic changes associated with heart failure, we investigated the effect of chronic angiotensin II stimulation on the fatty acid oxidation pathway in transgenic (TG) mice with targeted overexpression of angiotensinogen in the myocardium (TG1306/1R mice). TG1306/R1 mice progressively developed left ventricular hypertrophy. After 12 months, approximately half of the mice exhibited signs of heart failure including increased lung weight index [>+2 SD of age-matched wild-type (WT) mice] and 5-fold increase of myocardial brain natriuretic peptide expression. Myocardial mRNA and protein expression of peroxisome proliterator-activated receptor alpha (PPAR alpha) progressively decreased in both WT and TG1306/R1 mice during the 12 months observation period, but much more pronounced in TG1306/R1 mice. Concomitantly, mRNA expression of enzymes of fatty acid oxidation (medium-chain acyl CoA dehydrogenase, MCAD; carnitine palmitoyl transferase I, CPT-I) was reduced in TG1306/R1 compared with age-matched WT mice. However, protein expression of MCAD and CPT-I was decreased concomitantly only in TG mice with criteria of heart failure. Correspondingly, myocardial oxidation of palmitate, measured during ex vivo working heart perfusion, was reduced by 25% in TG1306/R1 mice with heart failure. These results demonstrate that angiotensin II-induced cardiac hypertrophy is associated with reduction of PPARa and of mRNA expression of enzymes of fatty acid metabolism relative to age-matched WT mice. However, both protein expression of fatty acid oxidation enzymes and the rate of fatty acid oxidation remain unchanged unless heart failure occurs, suggesting the involvement of posttranscriptional mechanisms in the metabolic changes associated with heart failure. (c) 2006 Elsevier Inc. All rights reserved.
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