VASCULAR SMOOTH MUSCLE CELLS IN DEVELOPMENT AND PROGRESSION OF VASCULAR DISEASE

血管平滑肌细胞（VSMC）和细胞外基质之间的相互作用 基质（ECM）在许多疾病的发展和进展中是重要的。 血管疾病 去分化VSMC的迁移和侵袭是细胞增殖和分化的重要环节。 这一过程中的一个关键事件。 正常情况下，静止的中膜VSMC 刺激迁移和增殖形成增生性新生内膜。 它们失去收缩（静止）表型并对PDGF产生反应。 我们 已经研究了VSMC分化和细胞增殖之间的关系。 运动性、侵袭性以及这些细胞与ECM的相互作用。 VSMC从 大鼠主动脉在组织培养塑料上容易增殖， 血清的 相反，在重建基底膜上培养的VSMC （基质胶）停止增殖，并迁移形成网络， 多细胞索状结构，如主动脉中所见。 我们 已经证明了去分化的VSMC具有很强的侵袭能力， 响应于PDGF的基质胶屏障。 相反，分化的VSMC 10-侵入性更小。 我们已经注意到胶原酶IV活性的作用， TGF-β、钙、体内年龄、基质金属蛋白酶（MMP）活性是 72 kD明胶酶mRNA积累减少，而 TGF-β处理的VSMC，净活性通过表达增加而降低 基质金属蛋白酶组织抑制剂（TIMPS）。 这些 观察表明，一个重要的作用和可能的机制， 血管平滑肌细胞和细胞外基质之间的相互作用， 许多血管疾病。

Interactions between vascular smooth muscle cells (VSMC) and extracellular matrix (ECM) are important in the development and progression of many vascular diseases. The migration and invasion of dedifferentiation VSMC is a key event in this process. Normally quiescent, medial VSMC are stimulated to migrate and proliferate forming a hyperplastic neointima. They lose their contractile (quiescent) phenotype and respond to PDGF. We have investigated the relationship between VSMC differentiation and the motility, invasiveness, and interaction of these cells with ECM. VSMC from rat aorta readily proliferated on tissue culture plastic in response to serum. In contrast, VSMC cultured on reconstituted basement membrane (Matrigel) ceased proliferating and migrated to form networks of multicellular cord-like structures such as those seen in the aorta. We have demonstrated a strong ability of dedifferentiated VSMC to invade a Matrigel barrier in response to PDGF. In contrast, differentiated VSMC are 10-fold less invasive. We have noted roles for collagenase IV activity, TGF-beta, calcium, in vivo age, matrix metalloproteinase (MMP) activity is decreased to a reduction in 72 kD gelatinase mRNA accumulation, while in TGF-beta-treated VSMC, net activity is reduced through increased expression of the tissue inhibitors of matrix metalloproteinases (TIMPS). These observations suggest an important role and possible mechanisms for the interactions between VSMC and ECM in the development and progression of many vascular diseases.