Bezafibrate Attenuates Pressure Overload-Induced Cardiac Hypertrophy and Fibrosis.
Si-Chi XuZhen-Guo MaWen-Ying WeiYu-Pei YuanQi-Zhu TangPublished in: PPAR research (2017)
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.
Keyphrases
- insulin resistance
- high glucose
- high fat diet induced
- diabetic rats
- drug induced
- left ventricular
- endothelial cells
- metabolic syndrome
- type diabetes
- oxidative stress
- signaling pathway
- coronary artery bypass
- skeletal muscle
- randomized controlled trial
- pulmonary artery
- aortic valve
- polycystic ovary syndrome
- physical activity
- high fat diet
- coronary artery disease
- tyrosine kinase
- acute coronary syndrome
- fatty acid
- liver fibrosis
- single molecule
- double blind
- pi k akt
- ejection fraction
- percutaneous coronary intervention