Open AccessEffects and mechanisms of PPARα activator fenofibrate on myocardial remodelling in hypertension
Author(s) -
Li ChuanBao,
Li XiaoXing,
Chen YuGuo,
Zhang Cheng,
Zhang MingXiang,
Zhao XueQiang,
Hao MingXiu,
Hou XiaoYang,
Gong MaoLei,
Zhao YuXia,
Bu PeiLi,
Zhang Yun
Publication year - 2009
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/j.1582-4934.2008.00484.x
Subject(s) - fenofibrate , medicine , endocrinology , activator (genetics) , pathogenesis , peroxisome proliferator activated receptor , c fos , saline , western blot , receptor , cardiac function curve , ventricular remodeling , chemistry , gene expression , myocardial infarction , heart failure , biochemistry , gene
Although peroxisome proliferator‐activated receptor α (PPARα) is highly expressed in the heart, the effects of PPARα on cardiac remodelling and the underlying mechanisms are unclear. The present study was undertaken to test the hypothesis that PPARα activator fenofibrate plays a key role in left ventricular hypertrophic remodelling via the formation of c‐fos/c‐jun heterodimers in spontaneous hypertensive rats (SHRs). Twenty‐four male 8‐week‐old SHRs were randomly divided into two groups, one group treated with oral saline ( n = 10) and another treated with oral fenofibrate (60 mg.kg −1 .d −1 , n = 14). Ten same‐aged Wistar–Kyoto (WKY) rats were selected as a normal control group. Using echocardiography, immunohistochemistry, co‐immunoprecipitation, Western blot analysis and real‐time RT‐PCR, we showed that the left ventricular wall thickness and significantly reduced and left ventricular diastolic function improved in SHRs treated with fenofibrate compared with SHRs treated with saline. Similarly, the excessive collagen deposition and the up‐regulation of collagen I, collagen III, c‐fos and c‐jun seen in SHRs receiving saline were significantly attenuated in SHRs receiving fenofibrate. In addition, fenofibrate markedly decreased the expression of AP‐1 and c‐fos/c‐jun heterodimers ( P < 0.01). These results demonstrated that PPARα activator fenofibrate may exert a protective effect on cardiac remodelling in SHRs by decreasing the expression of c‐fos and c‐jun and suppressing the formation of c‐fos/c‐jun heterodimers, which may further inhibit transcription of the downstream genes involved in the pathogenesis of left ventricular hypertrophy induced by hypertension.