Study On The SMC Proliferation, Apoptosis And Expression Of MGP, BMP-2 Induced By Oxidized LDL And The Effect Of Scorpion Venom

Ox-LDL is an important risk factor on inducing ofatherosclerosis. The proliferation and apoptosis in smooth musclecell is an important characteristic of atherosclerosis. There is aclose relationship between calcification and atherosclerosis.Calcification often indicates the formation of atherosclerosis.MGP and BMP-2 can regulate the progress of calcification.Ox-LDL can induce SMC proliferation and apoptosis. It also canaffect the expression of MGP and BMP-2.It is perhaps one of thereason how ox-LDL leads atherosclerosis. In this experimentscorpion venom can restrain the SMC proliferation and apoptosis.SV also can affect the expression of MGP and BMP-2. So we canconclude SV can resist AS. Method:Smooth muscle cell were incubated and treated with100mg/L ox-LDL and different concenteations (10, 20, 40mg/L)of SV for 24 hours. Then we checked the proliferation with MTT, apoptosis withTUNEL and the expression of MGP, BMP-2 withimmunohistochemistry and RT-PCR. Result: 1. Compared with control group, SMC proliferation andapoptosis of ox-LDL group significantly increased (P<0.05).2. After Incubating SMC with ox-LDL and differentconcenteations (10, 20, 40mg/L) of SV for 24 hours, SV cansignificantly decrease proliferation and apoptosis (P<0.05). Theeffect of SV1 (10mg/L) group is more infirmly than SV2 and SV3group. The percentage of apoptosis changed in a concentrationdependent manner.AS the SV concentration increased, thepercentage of apoptosis decreased.3. After Incubating SMC with 100mg/L ox-LDL for 24 hours,compared with control group, ox-LDL can significantlyupregulate the expression of BMP-2, underregulated theexpression of MGP with immuno-histochemistry and RT-PCR(P<0.05).4. After Incubating SMC with ox-LDL and differentconcenteations (10, 20, 40mg/L) of SV for 24 hours, comparedwith ox-LDL group, SV can significantly decrease the expressionof BMP-2, increase the expression of MGP (P<0.05) withimmuno-histochemistry. With RT-PCR we found SV cansignificantly decrease the expression of BMP-2, but we can notconclude if it changed in a concentration dependent manner. ASthe SV concentration increased, the expression of MGP increased(but P>0.05).Discussion:Ox-LDL can induce the progress of AS. Atheroscleroticplaque is an inflammation pathological change and there aremany inflammation factors during the process.Under thestimulation of ox-LDL, SMC can secrete some chemotacticfactors and adhesion molecules such as MCP-l , ICAM-l ,VCAM-l,lL-l,TNF. These chemotactic factors mediate theinducement of SMC proliferation and apoptosis by Ox-LDL. Inour experiment SMC proliferation and apoptosis of ox-LDLgroup significantly increased comparing with control group. Thisresult is consistent with other investigations. Thus it is importantto prevent SMC proliferation and apoptosis in clnical problem.Many investigations indicated that SMC can secret PGI2 ,TXA2 ,FIB,tPA,PAI. These vascular active factors can regulateSMC proliferation and apoptosis. SV can stimulate endothelialcells releasing PGI2, NO and upregulate the level of PA,underegulate radulate PAI. Recent study found K+ ion channelsplay important role in SMC phenotypes change. SV is oftenstudied in myocardium.SV can affect many ion channels, such asK+,Na+,Ca2+ ion channel.In this experiment SV can inhibitSMC proliferation and apoptosis.Perhaps this effect is mediatedthrough those pathway upwards.Calcification often signs the formation of atherosclerosis.MGP can inhibit vascular calcification. BMP-2 can inducecalcification. Someone found endothelial cells incubated withox-LDL can express more BMP-2,MGP than normal. LOX-1, thereceptor of ox-LDL, mediated this effect. Our experimentindicated SMCs incubated with ox-LDL can express more BMP-2,less MGP than normal. We found the reason how ox-LDL inducedAS, this is important for us to know much about AS.SV is a sort of Chinese traditional medicine, it has manyactive effects. Recently much more investigation on SV have putup than before in heare disease. We want to study how SV cureAS deeply. Compared with ox-LDL group, SV can significantlydecrease the expression of BMP-2, increase the expression ofMGP (P<0.05) with immuno-histochemistry. With RT-PCR wefound SV can significantly decrease the expression of BMP-2, butwe can not conclude if it changed in a concentration dependentmanner. AS the SV concentration increased, the expression ofMGP increased (but P>0.05). We will continue to study the trendin other experiments.Anyway, SMC proliferation and apoptosis is an importantcharacteristic of atherosclerosis. Calcification often indicates theformation of atherosclerosis. Ox-LDL is an important risk factoron inducing of atherosclerosis. Ox-LDL can induce SMCproliferation and apoptosis and affect the expression of MGP,BMP-2.SV can restrain the function of ox-LDL. Thus SV caninhibit atherosclerosis.Conclusion:Ox-LDL can induce SMC proliferation and apoptosis. SVcan inhibit this effect. In nomal, SMC can express MGP, BMP-2.Ox-LDL can increase the expression of BMP-2, decrease theexpression of MGP. SV can inhibit this effect, decrease theexpression of BMP-2, increase the expression of MGP. Thusthrough upregulating proliferation and apoptosis, affecting theexpression of MGP, BMP-2, ox-LDL can advance the progress ofAS. SV can restrain these effects of ox-LDL. Then SV canrestrain the progress of AS.