Study On The Role Of Ceramide In Angâ…¡-induced Endothelial Cells Apoptosis

Objectives: The mortality and morbidity of cardiovascular disease is increasing, so more studies is to clear the pathogenesis of cardiovascular disease. It is known that the endothelial cells (EC), which line the lumen of the blood vessels, are not passive bystanders but are active responders to stimuli like activated leukocytes and cytokines. The dysfunction of EC can provoke the progression of cardiovascular disease. Angiotensin II (AngII), as the main active peptide of the RAS, regulates both cellular and physiological responses in the cardiovascular system. However, AngII is also implicated in pathophysiological processes associated with vascular injury and repair. Ceramide belongs to a family of lipids known as sphingolipids, characterized by a sphingoid backbone and distinct head groups. Recently, more and more studys indicated that ceramide is a cellular lipid second messenger and is retained in the cytoplasm but enters the nucleus in response to various stimuli. It plays roles in cell proliferation,differentiate,growth inhibiting,especially in the inducing cellular apoptosis. Ceramide is urging apoptosis fatror, causing apoptosis in endothelial cell. It's biological effects make important roles in cardiovascular system.As a result, the purpose of the present study is to elucidate the role of ceramide in the apoptosis of EC induced by AngII.Methods: (1) The EC was treated with AngII alone. The apoptosis rates were measured by Tunel. In addition, ceramide,bax,bcl-2 were evaluated for their influence on the apoptosis of EC induced by Angâ…¡. The role of ceramide and bax,bcl- 2 in apoptosis of EC induced by Angâ…¡was evaluated.(2) After EC was induced with Angâ…¡and ceramide, the protein and gene expression of bax and bcl-2 were measured with Western blotting and reverse transcription-polymerase chain reaction (RT-PCR), and the roles and interrelations of ceramide,bax and bcl-2 in Angâ…¡were also observed.Results: (1) AngII can induce the apoptosis of EC in time- and dose-dependant manner. Fumonisin B1 can inhibite Angâ…¡-induced apoptosis.(2) The expression of bax mRNA and protein in EC treated with ceramide significantly increased,while the expression of bcl-2 mRNA and protein significantly depressed.Conclusions: In the process of apoptosis induced by Angâ…¡, ceramide plays an important role. Ceramide lies the upper stream of bax and bcl-2. Ceramide may induce apoptosis of endothelial cells by down-regulating bcl-2 and up-regulating bax and the ratio of bax/bcl-2.