e0344 The mechanism research of FRP inhibits endothelial cell apoptosis

Background Atherosclerosis is the most common cause of cardiovascular diseases in the world. Although the development of atherosclerosis appears to be the result of multiple maladaptive pathways, a particularly important factor in the pathogenesis of atherosclerosis is oxidised low density lipoprotein (ox-LDL), which contributes to endothelial damage. Data from our lab and others show that Follistatin related protein (FRP), which is expressed in the vasculature, has cardioprotective effects, suggesting that loss of FRP protection might play a role in the development of atherosclerosis. Objective In the present study, we determined whether FRP overexpression protects against endothelial cell (EC) damage, an intermediate endpoint for atherosclerosis. Methods We bred ApoE knockout (ApoE (−/−)) mice that were FRP+ transgenic (they overexpressed FRP. We compared them to control mice (their littermates). Human umbilical vein endothelial cells (HUVECs) were isolated and treated with ox-LDL and recombinant FRP. FRP-induced signal transduction and Bcl2 mRNA and protein stability were analysed. Results After 16 weeks, ApoE (−/−) FRP (+) mice had significantly fewer apoptotic endothelial cells than controls. In vitro experiments showed that the effect of FRP on EC apoptosis was mediated by upregulation of expression of the antiapoptotic protein Bcl2. Conclusion FRP overexpression maintains EC viability by preventing apoptosis via Bcl2 upregulation. FRP may be a novel therapeutic target for the prevention and treatment of vascular EC injury and of atherosclerosis.