Weissberg P L, Cary N R, Shanahan C M
Department of Medicine, University of Cambridge, Addenbrooke's Hospital, UK.
Blood Press Suppl. 1995;2:68-73.
Vascular smooth muscle cells (VSMCs) are involved in a number of vascular disease processes including hypertension and atherosclerosis. However, their role in the pathogenesis of vascular disease is largely undetermined. We and others have studied rat VSMCs in cell culture as a model for VSMC behaviour in vivo. In recent experiments we have applied molecular biological techniques to compare genes expressed by normal contractile VSMCs with those expressed by VSMCs which have undergone several passages in cell culture. Using differential screening of a cDNA library derived from cultured rat aortic VSMC RNA we identified seven genes which are preferentially expressed by contractile VSMCs; alpha-smooth muscle actin, gamma-smooth muscle actin, calponin, phospholamban, tropoelastin, SM22 alpha and CHIP28, and two which are preferentially expressed in passaged cells which have down-regulated their contractile proteins; osteopontin (OP) and matrix Gla protein (MGP). In situ hybridization studies have confirmed that calponin and SM22 alpha, are highly expressed by medial VSMCs in human coronary arteries with little or no expression in the atheromatous intima whilst the converse is true for OP and MGP. Studies by ourselves and others have confirmed that OP is a marker for proliferating rat VSMCs both in vitro and in vivo. However, the evidence that OP is expressed by proliferating human VSMCs is less convincing.
血管平滑肌细胞（VSMC）参与包括高血压和动脉粥样硬化在内的多种血管疾病过程。然而，它们在血管疾病发病机制中的作用在很大程度上尚未明确。我们和其他人已将细胞培养中的大鼠VSMC作为体内VSMC行为的模型进行研究。在最近的实验中，我们应用分子生物学技术比较正常收缩性VSMC表达的基因与在细胞培养中传代多次的VSMC表达的基因。通过对源自培养的大鼠主动脉VSMC RNA的cDNA文库进行差异筛选，我们鉴定出七个优先由收缩性VSMC表达的基因；α-平滑肌肌动蛋白、γ-平滑肌肌动蛋白、钙调蛋白、受磷蛋白、原弹性蛋白、SM22α和CHIP28，以及两个优先在已下调其收缩蛋白的传代细胞中表达的基因；骨桥蛋白（OP）和基质Gla蛋白（MGP）。原位杂交研究证实，钙调蛋白和SM22α在人冠状动脉的中层VSMC中高度表达，而在动脉粥样硬化内膜中几乎不表达或不表达，而OP和MGP则相反。我们自己和其他人的研究证实，OP在体外和体内都是增殖大鼠VSMC的标志物。然而，OP由增殖的人VSMC表达的证据不太令人信服。
