Inhibition Of Fenofibrate On Anglotensin â…¡-induced High Expresdon Of Osteopontin In Cardiac Fibroblasts

Fenofibrate is a synthetic peroxisome proliferator-activated receptorα(PPARα) agonist, which is generally used in clinical hypertriglyceridemiatreatment. Recently effects of fenofibrate besides adjusting blood lipid havegained increasing attention, such as regulating cardiac remodeling caused byhypertension or myocardial infarction, which can be partly explained by itscapability of anti-inflammatory and anti-fibrosis. Osteopontin (OPN), also knownas cytokine Eta-1, is a phosphorylated glycoprotein which can be synthesized andsecreted by a variety of cells including macrophages, neutrophils, dendritic cells,NK cells and T cells. Mature heart express only low levels of OPN under normalconditions, however, in many pathological conditions the expression of OPN wassignificantly up-regulated. OPN is able to enhance cardiac remodeling by meansof contributing to the growth and differentiation of cardiac fibroblasts, promotingcollagen synthesis, reducing MMP expression and activity, and promotingangiogenesis and cardiomyocyte hypertrophy. Therefore OPN is helpful toavoiding the excessive expansion of the ventricle and maintaining cardiacfunction. Excessive changes in heart structure will bring negative impacts on cardiac systolic and diastolic function, consequently regulating the expression ofOPN in different stages of cardiac remodeling may have a wide prospect ofclinical application. This study is designed to investigate the effects of fenofibrateon osteopontin expression in cardiac fibroblasts and to further explore itspharmacological effect in cardiovascular system.AIM: To investigate the effects of fenofibrate, peroxisomeproliferator-activated receptorα(PPARα) agonist, on the up-regulation ofangiotensinⅡ(AngⅡ)-induced osteopontin in rat cardiac fibroblasts. Methods:Isolated cardiac fibroblasts of neonatal Sprague-Dawley rat were pretreated withvarious concentrations of fenofibrate (0, 25, 50 and 100μmmol/L) for 1 hour.Then AngⅡwere added into cells for 24 hours. The expression of osteopontinwas measured by real-time quantitative RT-PCR and Western blot, separately.Results: Significant inhibitory effects of fenofibrate on AngⅡ-induced highexpression of osteopontin were observed in cardiac fibroblasts and the effect wasdose dependent (p<0.05). Conclusion: The present data suggests that fenofibratecan down-regulate the level of osteopontin in rat cardiac fibroblasts, which mayexplain the anti-inflammatory and anti-fibrosis effects of fenofibrate in thecardiovascular system.