ABSTRACT
Diabetic cardiomyopathy refers to the heart disease without coronary artery disease and hypertension,diabetic patients with ventricular dysfunction.The molecular mechanism of diabetic cardiomyopathy remains unclear.Protein and lipid kinase phosphoinositol 3-kinase (PI3Ks) are thought to regulate cardiac damage in diabetes mellitus.This article reviews the role of PI3K subtypes and downstream signal transduction in the pathogenesis of diabetic cardiomyopathy,including cardiac metabolic regulation,contractility,hypertrophy,cardiomyocyte death and inflammation.
ABSTRACT
Objective To investigate the effects of amyloid-β (Aβ)25-35 on endoplasmic reticulum (ER) stress and apoptosis in cultured rat cardiomocytes,and to elucidate the role of ER stress in the injury of cardiomocytes induced by Aβ25-35.Methods The isolated rat myocardial cells were cultured in vitro.Following stimulation of Aβ25-35 with different dose,the survival ratio was observed with methyl thiazolyl tetrazolium (MTT) method.Hoechst33258 staining was used to observe the morphology of apoptotic changes.The percentage of apoptotic cardiomyocytes was quantified with flow cytometry.The expressions of ER stree proteins,including X box-binding protein-1 (XBP-1),glucose-regulated protein 78 (GRP78),and CCAAT/enhancer-binding protein homologous protein (CHOP) were measured with Western blot.The cleaved caspase-3 and cleaved poly (ADP-ribose) polymerase (PARP) were measured with Western blot.Results Aβ25-35 decreased the survival ratio and induced the apoptosis of cultured rat cardiomocytes in dose-dependent mode.Meanwhile,Aβ25-35 increased the expressions of ER stree proteins,including XBP-1,GRP78,and CHOP.Aβ25-35 increased the expressions of cleaved caspase-3 and cleaved PARP.Conclusions Aβ25-35 could induce the apoptosis of rat cardiomyocytes,which were involved in ER stress possibly.This study might provide a new strategy for clinical treatment of Alzheimer's disease (AD)-associated myocardial injury.
