Peroxisome Proliferator-Activated ReceptorαReduces Endothelin-1-Caused Cardiomyocyte Hypertrophy by Inhibiting Nuclear Factor-κB and Adiponectin.
Peroxisome proliferator-activated receptorα(PPARα) plays a role in the pathogenesis of cardiac hypertrophy, although its underlying mechanism remains unclear. The purpose of this study was to evaluate the effect of PPARαactivation on endothelin-1- (ET-1-) caused cardiomyocyte hypertrophy and explore its underlying mechanisms. Human cardiomyocytes (HCMs) were cultured with or without ET-1, whereafter the inhibitory effects of fenofibrate, a PPARαactivator, on cell size and adiponectin protein were tested. We examined the activation of extracellular signal-regulated kinase (ERK) and p38 proteins caused by ET-1 and the inhibition of the ERK and p38 pathways on ET-1-induced cell size and adiponectin expression. Moreover, we investigated the interaction of PPARαwith adiponectin and nuclear factor-κB (NF-κB) by electrophoretic mobility shift assays and coimmunoprecipitation. ET-1 treatment significantly increased cell size, suppressed PPARαexpression, and enhanced the expression of adiponectin. Pretreatment with fenofibrate inhibited the increase in cell size and enhancement of adiponectin expression. ET-1 significantly activated the ERK and p38 pathways, whereas PD98059 and SB205380, respectively, inhibited them. Our results suggest that activated PPARαcan decrease activation of adiponectin and NF-κB and inhibit ET-1-induced cardiomyocyte hypertrophy.
Division of Cardiology, Cheng-Hsin General Hospital, Taipei, Taiwan; Institute of Clinical Medicine, Faculty of Medicine, Institute of Pharmacology, and Cardiovascular Research Centre, National Yang-Ming University, Taipei, Taiwan.
Hsu-Lung
HL
Jen
Department of Respiratory Therapy, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Po-Len
PL
Liu
Graduate Institute of Integrated Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan; Department of Psychology, College of Medical and Health Science, Asia University, Taichung, Taiwan.
Yung-Hsiang
0000-0002-8756-5113
YH
Chen
Division of Cardiology, Cheng-Hsin General Hospital, Taipei, Taiwan; Institute of Clinical Medicine, Faculty of Medicine, Institute of Pharmacology, and Cardiovascular Research Centre, National Yang-Ming University, Taipei, Taiwan.
Wei-Hsian
0000-0001-8137-7173
WH
Yin
Institute of Clinical Medicine, Faculty of Medicine, Institute of Pharmacology, and Cardiovascular Research Centre, National Yang-Ming University, Taipei, Taiwan; Department of Medical Research, Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
Jaw-Wen
JW
Chen
Institute of Clinical Medicine, Faculty of Medicine, Institute of Pharmacology, and Cardiovascular Research Centre, National Yang-Ming University, Taipei, Taiwan; Department of Medical Research, Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
Shing-Jong
SJ
Lin
D052242:Adiponectin / Q000378:metabolism*; D015153:Blotting, Western; D002478:Cells, Cultured; D024202:Electrophoretic Mobility Shift Assay; D019332:Endothelin-1 / Q000494:pharmacology*; D011345:Fenofibrate / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D006801:Humans; D006984:Hypertrophy / Q000378:metabolism*; D047468:Immunoprecipitation; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism*; D047493:PPAR alpha / Q000819:agonists / Q000378:metabolism*
D052242:Adiponectin; D019332:Endothelin-1; D016328:NF-kappa B; D047493:PPAR alpha; D011345:Fenofibrate