Effects of extracellular matrix on changes of phenotype and gene expression in vascular smooth muscle cells

我们观察了内皮剥脱对血管平滑肌细胞(SMC)表型变化的影响。剥脱后2天或5天的主动脉外植体的SMC生长速度明显高于未经处理的SMC。剥脱5d后，主动脉SMC也可观察到乙酰化低密度脂蛋白的清除途径和生长刺激因子(S)的自分泌，而未经处理的SMC则未见此现象。这些获得性病理特征与动脉粥样硬化病变的内膜SMC相似。这些结果表明，表型改变的临界点是在治疗后很早的时间，它发生在新生内膜形成之前的主动脉中层。另有实验表明，糖尿病兔主动脉SMC表达PDGF-β，对PDGF-AB、PDGF-BB或全血清液反应迅速。其他实验表明，肿瘤坏死因子-α刺激SMC由收缩表型向合成型转化。提示中膜SMC对动脉内膜损伤的早期反应对调控动脉粥样硬化形成的后续步骤具有重要意义。我们现在正在进行实验，以阐明内皮剥脱后表型改变的初始阶段基因表达的变化。之后，将进一步阐明SMC与细胞外基质的相互作用对SMC表型的影响，以评估调控SMC表型变化早期步骤的可能性。

We have examined effects of endothelial denudatio of phenotype cange of vasclar smooth muscle cells(SMC). Outgrowth rate of SMC from explants of aorta 2 or 5 days after denudation was much higher than that from untreated aorta. Scavenger pathway for acetylated low density lipoprotein and autocrine secretion of growth stimulator(s) were also observed inSMC from the aorta 5 days after denudation but not in SMC from untreated aorta. These acquired pathological ahcracters were similar to those of intimal SMC from atherosclerotic lesions. These results suggest that critical point of the phenotype change is at very early time after the treatment and it occurs within the aortic media before formation of neo-intima. another experimants revealed that SMCfrom aorta of diabetic rabbits expressed PDGF beta and the SMC showed rapid growthrate responded to PDGF-AB, PDGF-BB or whole serum. The other experiments showed that tumor necrosis factor-alpha stimulated SMC to change their phenotype from contractile to synthetic type. These data suggest that early response of medial SMC to intimal injury must ve very important to regulate the following steps to formation of atherosclerosis. We are now engaging in experiments to clarify changes of gene expression in the initial step of phenotype change after endothelial denudation. After that, effects of interaction between SMC and extracellular matrix on the phenotype of SMC will be further elucidated to assess possibilities to regulate the early step of phenotype change.