EFFECT OF ERK1/2 SIGNAL TRANSDUCTION PATHWAY IN VASCULAR ENDOTHELIAL CELL APOPTOSIS

Objectives To explore the changes in extracellar signal-regulated protein kinase (ERK1/2) in endothelial cell senescence induced by AngiotensinII at the different time courses, and its possible molecular mechanism. Methods Human umbilical vein endothelial cell (HUVEC) were cultured in vitro and intervened by AngII. HUVEC were divided into two groups, the control group, AngII group (stimulated by AngII 10−6 mol/l for 48 h). Human HUVECs were cultured in vitro and intervened by AngII. The cell living rate was observed by methyl thiazolyl tetrazolium (MTT), B gal staining and cell cycle analysis were used to identify cell aging status. Cell senescence was used to study by transmission electric microscopy. The expressions of apoptosis-association genes Bcl-2, Bax were detected by immunocytochemistry and ERK1/2 levels were detected by Western-blotting at different time points. Results 10−6 mol/l AngiotensinII stimulation stimulated cell senescence. The cell living rate by AngII-induced cells was (81.9%±4.1%, p<0.01), the positive cell number of ß-gal staining was significantly higher in AngII-induced cells than that in the control cells (80.10%±6.81% vs 0.18%±0.04%, p<0.01); the cell cycle was at G0-G1 (91.36%±6.45%, p<0.01), S phase and G2/M phase were a tendency to disappearance in AngII-induced cells (6.62%±0.42% vs 2.12%±0.33%, p<0.01), the senescent cells significantly increased under transmission electric microscopy. Bcl-2mRNA levels were time-dependently decreased, the radio of Bcl-2/Bax was decreased markedly p<0.05). Phosphorylation of ERK1/2 began to increase and reach the peak at 24 h p<0.01). Conclusions Cell senescence is possibly important factor for atherosclerosis. One of its molecular mechanisms might be associated with decreasing the expression level of Bcl-2 and the radio of Bcl-2/Bax. There is a probability that activated ERK1/2 signal pathway is involved in the process of pathologic and physiologic reaction in the senescence of endothelial cell induced by AngiotensinII.