Abstract
Background. Peroxisome proliferator-activated receptor-α (PPAR-α) is closely associated with the development of cardiac hypertrophy. Previous studies have indicated that bezafibrate (BZA), a PPAR-α agonist, could attenuate insulin resistance and obesity. This study was designed to determine whether BZA could protect against pressure overload-induced cardiac hypertrophy. Methods. Mice were orally given BZA (100 mg/kg) for 7 weeks beginning 1 week after aortic banding (AB) surgery. Cardiac hypertrophy was assessed based on echocardiographic, histological, and molecular aspects. Moreover, neonatal rat ventricular cardiomyocytes (NRVMs) were used to investigate the effects of BZA on the cardiomyocyte hypertrophic response in vitro. Results. Our study demonstrated that BZA could alleviate cardiac hypertrophy and fibrosis in mice subjected to AB surgery. BZA treatment also reduced the phosphorylation of protein kinase B (AKT)/glycogen synthase kinase-3β (GSK3β) and mitogen-activated protein kinases (MAPKs). BZA suppressed phenylephrine- (PE-) induced hypertrophy of cardiomyocyte in vitro. The protective effects of BZA were abolished by the treatment of the PPAR-α antagonist in vitro. Conclusions. BZA could attenuate pressure overload-induced cardiac hypertrophy and fibrosis.
Highlights
Cardiac hypertrophy is defined as an increase in cardiomyocyte size, interstitial fibrosis, and cardiac dysfunction [1, 2]
The mice subjected to aortic banding (AB) surgery developed deteriorated cardiac function, as evidenced by the increase in LVDD and the reduction in left ventricular fractional shortening (LVFS) and ejection fraction (LVEF) (Figure 1(a))
Our research demonstrated that BZA can inhibit cardiac hypertrophy in vivo and in vitro
Summary
Cardiac hypertrophy is defined as an increase in cardiomyocyte size, interstitial fibrosis, and cardiac dysfunction [1, 2]. Accumulating evidence indicates that protein kinase B (AKT)/glycogen synthase kinase-3β (GSK3β) and mitogen-activated protein kinases (MAPKs) play key roles in the development of cardiac hypertrophy [4]. MAPKs were closely associated with the development of the hypertrophic response. Peroxisome proliferator-activated receptor-α (PPAR-α) is closely associated with the development of cardiac hypertrophy. This study was designed to determine whether BZA could protect against pressure overload-induced cardiac hypertrophy. Neonatal rat ventricular cardiomyocytes (NRVMs) were used to investigate the effects of BZA on the cardiomyocyte hypertrophic response in vitro. Our study demonstrated that BZA could alleviate cardiac hypertrophy and fibrosis in mice subjected to AB surgery. BZA treatment reduced the phosphorylation of protein kinase B (AKT)/glycogen synthase kinase-3β (GSK3β) and mitogen-activated protein kinases (MAPKs).
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