期刊
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
卷 299, 期 3, 页码 H690-H698出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpheart.01032.2009
关键词
peroxisome proliferator-activated receptor gamma; adiponectin; thiazolidinediones; regulation of gene expression; cardiac hypertrophy; type 2 diabetes
资金
- Michigan Tri-Technology Corridor [MLSC-27]
- National Institute of Diabetes and Digestive and Kidney Diseases [DK-062102]
- Pfizer Global Research Development
- American Heart Association [0620014Z]
Amin RH, Mathews ST, Alli A, Leff T. Endogenously produced adiponectin protects cardiomyocytes from hypertrophy by a PPAR gamma-dependent autocrine mechanism. Am J Physiol Heart Circ Physiol 299: H690-H698, 2010. First published July 9, 2010; doi:10.1152/ajpheart.01032.2009.-In experimental animal and cell culture models, activation of peroxisome proliferator-activated receptor (PPAR) gamma in heart has been shown to have beneficial effects on cardiac function and cardiomyocyte physiology. The goal of this study was to identify the signaling pathway by which PPAR gamma activation protects cardiomyocytes from the deleterious effects of hypertrophic stimuli. In primary cardiomyocyte cultures, we found that genetic or pharmacological activation of PPAR gamma protected cells from cardiac hypertrophy induced by alpha-adrenergic stimulation. Examination of gene expression in these cells revealed a surprising increase in the expression of adiponectin in cardiomyocytes and secretion of the high-molecular-weight form of the hormone into media. Using RNAi to block PPAR gamma-induced adiponectin production or adiponectin receptor gene expression, we found that the PPAR gamma-mediated anti-hypertrophic effect required cardiomyocyte-produced adiponectin, as well as an intact adiponectin signaling pathway. Furthermore, mice expressing constitutive-active PPAR gamma and cardiomyocyte specific adiponectin expression were protected from high-fat diet-induced cardiac hypertrophy and remodeling. These findings demonstrate that functional adiponectin hormone can be produced from the heart and raise the possibility that beneficial effects of PPAR gamma activation in heart could be due in part to local production of adiponectin that acts on cardiomyocytes in an autocrine manner.
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