The Effect Of Herbesser On Proliferation And Apoptosis Of Vascular Smooth Muscle Cell

Imbalance between proliferation and apoptosis of VSMC plays a critical role in the development of atherosclerosis and restenosis following PCI. In the early stages of atherosclerosis, the hyperproliferation and short-apoptosis lead to increasing of cells'number, VSMC migrstages to the vascular endothelium, becomes foam cell by swallowing the lipid, and forms the atheromatous plaque. In addition, VSMC releases cell factors to elevate the proliferation rate of VSMC itself, then promotes the development of atherosclerosis. VSMC proliferation and extracellular matrix deposition leads to the restenosis following PCI.Evidence-based Medicine have demonstrated that calcium channel blocker inhibits atherosclerosis. Hebesser is a kind of calcium channel blocker, we investigate whether hebesser has the role to inhibit proliferation and promote apoptosis of VSMC induced by AngⅡin this experiment, in order to offer the evidence of treating atherosclerosis and restenosis following PCI by hebesser.PURPOSE:This experiment investigates the change in proliferation and apoptosis of vascular smooth muscle cell induced by AngⅡ, and the change in expression of Bcl-2,Bax,Fas,P53. Then we approach the influence and mechanism of hebesser in proliferation and apoptosis.METHODS:Divide VSMC into 5 groups at random. The groups are respectively named with control group, modal group( AngⅡ10-7mol/L), modal+hebesser groups, among the model+hebesser groups, hebesser is divided to 10-5,10-6,10-7mol/L different density. Every group is cultured 48 hours. To determine the cell proliferation by MTT, to detect the cell cycle by flow cytometry, to detect theapoptosis by TUNEL, to evaluate the expression of Bcl-2,Bax,Fas,P53 by RT-PCR. The experimental data was denoted to mean±standard deviation( x±s), use analysis of variance to statistics analyze the numerus compare of each group.RESULTS:1,The VSMC proliferation rate after hebesser is lower than that after AngII. It shows inverse proportion to the density of hebesser.2,Constituent ratio of VSMC G0/G1 cell cycle after hebesser is higher than that after AngII. It shows direct proportion to the density of hebesser. Constituent ratio of VSMC S cell cycle,G2/M cell cycle and proliferation index after hebesser is lower than those after AngII. The S cell cycle shows inverse proportion to the density of hebesser, the G2/M cell cycle doesn`t relate to the density of hebesser.3,The VSMC apoptosis rate after hebesser is higher than that after AngII. It shows direct proportion to the density of hebesser.4,The Bcl-2 expression of VSMC after hebesser is lower than that after AngII. It shows inverse proportion to the density of hebesser.5,The Bax,Fas expression of VSMC after hebesser is higher than those after AngII. They show direct proportion to the density of hebesser.6,The P53 expression of VSMC after high and middle density hebesser is higher than those after AngII. They show direct proportion to the density of hebesser. But there is no difference between the P53 expression of VSMC after low density hebesser and that after AngII.CONCLUSION:1,Hebesser inhibits the proliferation of VSMC.2,Hebesser arrests the cell cycle of VSMV,it inhibits the G0/G1 cell cycle to enter the S cell cycle.3,Hebesser promotes the apoptosis of VSMC.4,Hebesser decreases Bcl-2 expression and increases Bax,Fas,P53 expression.RESEARCH SIGNIFICANCE:To prevent and treat atherosclerosis and restenosis following PCI is a hot spot in cardiovascular research domain, Hebesser is used to treat hypertension and angina pectoris as a kind of calcium channel blocker. This experiment demonstrates that hebesser inhibits proliferation and promotes apoptosis of VSMC. This experiment offers a new experimental and theoretical evidence to further develop hebesser to treat atherosclerosis and restenosis following PCI.