期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 100, 期 3, 页码 1226-1231出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0336724100
关键词
-
资金
- NHLBI NIH HHS [F32 HL067575, P01 HL013851, P01 HL13851, P01 HL57278, P01 HL057278] Funding Source: Medline
- NIDDK NIH HHS [P30 DK052574, R01 DK045416, P30 DK056341, P30 DK52574, P30 DK56341, R01 DK45416] Funding Source: Medline
To explore the role of peroxisome proliferator-activated receptor alpha (PPARalpha)-mediated derangements in myocardial metabolism in the pathogenesis of diabetic cardiomyopathy, insulinopenic mice with PPARa deficiency (PPARalpha(-/-)) or cardiac-restricted overexpression [myosin heavy chain (MHC)-PPAR] were characterized. Whereas PPARalpha(-/-) mice were protected from the development of diabetes-induced cardiac hypertrophy, the combination of diabetes and the MHC-PPAR genotype resulted in a more severe cardio-myopathic phenotype than either did alone. Cardiomyopathy in diabetic MHC-PPAR mice was accompanied by myocardial longchain triglyceride accumulation. The cardiomyopathic phenotype was exacerbated in MHC-PPAR mice fed a diet enriched in triglyceride containing long-chain fatty acid, an effect that was reversed by discontinuing the high-fat diet and absent in mice given a medium-chain triglyceride-enriched diet. Reactive oxygen intermediates were identified as candidate mediators of cardiomyopathic effects in MHC-PPAR mice. These results link dysregulation of the PPARalpha gene regulatory pathway to cardiac dysfunction in the diabetic and provide a rationale for serum lipid-lowering strategies in the treatment of diabetic cardiomyopathy.
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