VASCULAR SMOOTH MUSCLE CELLS IN DEVELOPMENT AND PROGRESSION OF VASCULAR DISEASE

几种血管疾病的发展和进展取决于 血管平滑肌细胞（VSMC）的迁移和增殖， 它们与细胞外基质（ECM）的相互作用。 我们发现 以前，这种相互作用部分是由于入侵， VSMC对PDGF的反应是重建基底膜（Matrigel）。 分化（去分化）的VSMC表现出五倍于 与融合后（分化）VSMC相比的侵袭性。 我们 已经证明细胞内钙动力学在 在VSMC侵袭中起作用，但在趋化性中不起作用。 趋化性反映了 细胞附着于基质并响应于细胞粘附而迁移的能力。 化学引诱物 化学侵袭需要细胞的额外能力 来降低屏障。 我们已经证明了72 KD的IV型和92 KD的 侵袭性VSMC中IV胶原酶活性的酶谱法。 北方斑点 分析表明72 KD IV型胶原酶的mRNA，而不是92 KD IV型胶原酶。 侵袭性VSMC也表达 基质金属蛋白酶组织抑制剂（TIMPs）-反映 积极和消极调节者之间平衡的重要性。 使用72 KD IV型胶原酶的抗血清的化学侵袭测定， 非免疫血清和92 KD IV型胶原酶的抗血清， 研究表明，VSMC对PDGF的侵袭反应是由72 KD IV型胶原酶。 趋化性较少依赖于72 KD IV型 胶原酶 因为这些胶原酶以酶原形式分泌， ECM的降解需要活化。 实验结果 使用BAPTA（细胞内钙的螯合剂）和离子霉素（a 钙离子载体）表明钙在这种激活中可能是重要的。

The development and progression of several vascular diseases depend on the migration and proliferation of vascular smooth muscle cells (VSMC) and their interaction with extracellular matrix (ECM). We have found previously that this interaction is due in part to the invasion of reconstituted basement membrane (Matrigel) by VSMC in response to PDGF. Proliferative (dedifferentiated) VSMC exhibit fivefold greater invasiveness as compared with post-confluent (differentiated) VSMC. We have demonstrated that intracellular calcium dynamics play an important role in VSMC invasion but not in chemotaxis. Chemotaxis reflects the ability of cells to attach to a substrate and migrate in response to a chemoattractant. Chemoinvasion requires the additional ability of cells to degrade a barrier. We have demonstrated 72 KD type IV and 92 KD type IV collagenase activity by zymography in invasive VSMC. Northern blot analyses have indicated mRNA for 72 KD type IV collagenase but not 92 KD type IV collagenase in these cells. Invasive VSMC also express mRNA for the tissue inhibitors of matrix metalloproteinases (TIMPs) - reflecting the importance of a balance between positive and negative regulators. Chemoinvasion assays employing antiserum to the 72 KD type IV collagenase, nonimmune serum, and antiserum to the 92 KD type IV collagenase, have demonstrated that VSMC invasion in response to PDGF is mediated by the 72 KD type IV collagenase. Chemotaxis is less dependent on the 72 KD type IV collagenase. Because these collagenases are secreted in zymogen form, activation is required for degradation of ECM. Experimental results employing BAPTA (a chelator of intracellular calcium) and ionomycin (a calcium ionophore) suggest calcium may be important in this activation.