Mechanisms of proliferation and migration of human vascular smooth muscle cells

初步成功的经皮冠状动脉腔内成形术(PTCA)后，30-40%的患者会发生再狭窄，因此仍然是一个重要的临床问题。在绝大多数情况下，以平滑肌细胞为主要细胞成分的纤维细胞反应是血管再狭窄的基本形态基础，平滑肌细胞的迁移、增殖以及细胞外基质成分的合成与其细胞骨架特征密切相关。到目前为止，大多数信息都是从实验研究中获得的，人类血管平滑肌细胞迁移和增殖的机制尚不清楚。本研究首次证明，PDGE-A和PDGF-B链mRNAs在PTCA术后人类冠状动脉的修复部位都有表达(Ueda M等人。Am J Pathol 1996)。这项研究还显示了血小板衍生生长因子-B和血小板衍生生长因子-β受体蛋白在人类血管成形术后修复部位的表达(Tanizawa，S等。心脏1996年)。这些发现有力地表明，血小板衍生生长因子参与了人类冠状动脉平滑肌细胞的迁移和增殖过程。此外，本研究还证明，Tenascin的上调可能在人类平滑肌细胞的迁移和表型改变中发挥作用(Tanabe，S等人)。Transpl Int 1996)。本研究还首次证明，C型利钠肽(CNP)是一种有效的平滑肌细胞抑制物，在人类冠状动脉内膜细胞中表达，并在动脉粥样硬化形成中具有功能意义(Naruko T等人)。发行量(1996年)。最后，我们的研究表明，在PTCA部位的平滑肌细胞迁移和增殖过程中，平滑肌细胞表现出未分化的特征，这表明平滑肌肌球蛋白重链(Aikawa M et at.)的表达发生了变化。

Restenosis after an initial successful percutaneous transluminal coronary angioplasty (PTCA) occurs in 30-40% of patients and thus remains a significant clinical problem. In the vast majority, a fibrocellular tissue reaction with smooth muscle cells, as the prime cellular component, is the underlying morphologic substrate of restenosis.Migration and proliferation of smooth muscle cells as well as synthesis of extracellular matrix components, relate closely to their cytoskeletal features. Most information thus far has been obtained from experimental studies, and the mechanisms that underlie migration and proliferation of human smooth muscle cells are unclear still.The present study demonstrates, for the first time, that both PDGE-A and PDGF-B chain mRNAs are expressed at sites of repair in human coronary arteries after PTCA (Ueda M et al. Am J Pathol 1996). This study also shows the expression of PDGF-B and PDGF-beta receptor proteins at sites of postangioplasty repair in humans (Tanizawa S et al. Heart 1996). These findings strongly suggest that PDGF is involved in the process of migration and proliferation of smooth muscle cells in human coronary arteries.The present study, moreover, documents that up-regulation of tenascin may play a role in the migration and phenotypic modulation of smooth muscle cels in humans (Tanabe S et al. Transpl Int 1996). The present study also demonstrates, for the first time, that C-type natriuretic peptide (CNP), which is a potent inhibitor of smooth muscle cells, is expressed in intimal cells of human coronary arteries, and has functional significance in atherogenesis (Naruko T et al. Circulation 1996). Finally, our study shows that, during smooth muscle cell migration and proliferation at the site of PTCA,smooth muscle cells show features of an undifferentiated state, indicated by altered expression of smooth muscle myosin heavy chain (Aikawa M et at., Circulation in press).