ABSTRACT
Cardiovascular disease is a growing major global public health problem. Oxidative stress is regarded as one of the key regulators of pathological physiology, which eventually leads to cardiovascular disease. However, mechanisms by which FGF-2 rescues cells from oxidative stress damage in cardiovascular disease is not fully elucidated. Herein this study was designed to investigate the protective effects of FGF-2 in H2O2-induced apoptosis of H9c2 cardiomyocytes, as well as the possible signaling pathway involved. Apoptosis of H9c2 cardiomyocytes was induced by H2O2 and assessed using methyl thiazolyl tetrazolium assay, Hoechst, and TUNEL staining. Cells were pretreated with PI3K/Akt inhibitor LY294002 to investigate the possible PI3K/Akt pathways involved in the protection of FGF-2. The levels of p-Akt, p-FoxO3a, and Bim were detected by immunoblotting. Stimulation with H2O2 decreased the phosphorylation of Akt and FoxO3a, and induced nuclear localization of FoxO3a and apoptosis of H9c2 cells. These effects of H2O2 were abrogated by pretreatment with FGF-2. Furthermore, the protective effects of FGF-2 were abolished by PI3K/Akt inhibitor LY294002. In conclusion, our data suggest that FGF-2 protects against H2O2-induced apoptosis of H9c2 cardiomyocytes via activation of the PI3K/Akt/FoxO3a pathway.
Subject(s)
Apoptosis/drug effects , Fibroblast Growth Factor 2/physiology , Forkhead Box Protein O3/metabolism , Hydrogen Peroxide/toxicity , Myocytes, Cardiac/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Animals , Bcl-2-Like Protein 11/metabolism , Cell Line , Phosphorylation , Protein Transport , RatsABSTRACT
Cardiovascular disease (CVD) is the leading cause of death worldwide, with aging as the key independent risk factor. Effective interventions are necessary to delay aging. Sirtuin1 (SIRT1), a NAD(+)-dependent histone deacetylase, is closely related to lifespan extension. SIRT1 exerts beneficial effects on aging and age-related diseases, such as atherosclerosis. In this review, we summarize the current knowledge on the functions of SIRT1 in cardiovascular aging, focusing on the underlying molecular mechanisms, including inhibition of oxidative stress and inflammation, and induction of autophagy. We also demonstrate that moderate up-regulation or activation of SIRT1 in cardiovascular aging and age-related CVD may confer important application values.
