Class A Scavenger Receptor Protects Heart From Pressure Overload-induced Cardiac Hypertrophy And Fibrosis In Mice

Cardiac hypertrophy,an increase in heart muscle mass,reflects a remodeling of the myocardium in response to mechanical stress and various stimuli.Macrophage scavenger class A receptor(SR-A)is trimeric,integral membrane glycoproteins that bind an unusually broad array.of macromolecular ligands.It has been reported that SR-A is associated with many cardiovascular diseases such as atherosclerosis and myocardial infarction.But the functions of SR-A in cardiac hypertrophy and cardiac remodeling are unknown.In this study,we hypothesized that SR-A may protects heart from pressure overload-induced cardiac hypertrophy and fibrosis in mice.In order to demonstrate SR-A is required for cardiac hypertrophy,WT mice were treated with transverse aortic constriction(TAC),after four weeks,we found that the expression level of SR-A in heart is higher than sham group.Then,both SR-A deficient mice and wild-type mice were treated with TAC,after four weeks,the characteristics of cardiac hypertrophy were analyzed by echocardiography,histology,and gene expression.As a result,we found that left ventricular hypertrophy and fibrosis,Collagen deposition,and myofibroblast transformation of cardiac fibroblasts in response to pressure overload by TAC were exaggerated in SR-A deficient mice compared with wild-type controls in vivo.In vitro,we separated cardiac fibroblasts from both SR-A deficient mice and wild-type mice,and then treated cardiac fibroblasts with angiotensin II,then analyzed the expression levels of a-SMA,Vimentin,Collagen.I,Collagen III,as a result,we found that SR-A inhibited Ang?-induced myofibroblast transformation,proliferation,Collagen synthesis in cardiac fibroblasts.In conclusion,this study indicates that SR-A may protect heart from pressure overload-induced cardiac hypertrophy,and SR-A may inhibited cardiac fibrosis by inhibiting myofibroblast transformation,proliferation,and Collagen.