The Molecular Pathological Mechanism Of Preventive Effect Of Human ApoAI On Murine Vascular Smooth Muscle Cell Proliferation And Lipid Deposition Induced By Ox-LDL

Atherosclerosis (AS) is the pathologic basis for cardio-cerebral diseases which are noticed as the leading cause of death in many countries including China. Study on the pathogenesis and prevention of AS has always been a high priority.In recent years, accumulating evidences indicated that both inflammation and immunity are involved in the pathogenesis of atherosclerosis. In addition, atherosclerosis is also a multigenic disease. Among the environmental risk factors already realized, oxidized low density lipoprotein (ox-LDL) is known as a key atherogenic effector; The human apoA-I gene transgenic C57BL/6 mouse model adopted in this study was an animal model established in our laboratory in 1997 containing a mouse metallothionein-1(MT-1) promotor and was stable. Data obtained from both animal and cellular experiments have shown that the transgenic mouse model was highly atherosclerosis resistant in vivo after a high-cholesterol intake and the amount of cholesterol uptake was much less and the clearance rate increased in vSMC originated from the model' s aortae in vitro after ox-LDL stimulation respectively.In this study, subtractive hybridization and SMART technique were used to isolate genes expressed during this process, thus, some insights were manifested about the molecular basis of the preventive effect of human apoA-I on vascular smooth muscle cells (vSMC) proliferation after an ox-LDL stimulation or damage.All the transgenic mice used were identified beforehand to be h-apoA-I integrated and able to express human apoA-I mRNA using PCR and Northern blot.