Herman I M
Tufts University Health Science Schools, Program in Cell, Molecular and Developmental Biology, Boston, Mass.
Haemostasis. 1990;20 Suppl 1:166-77. doi: 10.1159/000216176.
Whereas vascular smooth muscle cell-extracellular matrix interactions have been intensively studied, our knowledge regarding the role that matrix plays in regulating the growth state and contractile phenotype of vessel wall cells is fragmentary. Of particular interest has been the demonstrable ability of (1) heparin to selectively inhibit vascular smooth muscle cell growth in vitro; (2) aortic endothelial cells to produce a heparin-like inhibitor of vascular smooth muscle cells, and (3) heparin to reverse smooth muscle cell proliferation in arteries that have been experimentally denuded of their endothelium. Recent work from our laboratory indicates that the endothelial cell synthesized extracellular matrix alters growth rate and heparin sensitivity of vascular smooth muscle cells. Whereas endothelial cell synthesized matrices that contain collagen and fibronectin promote smooth muscle cell growth, matrices containing heparan sulfate proteoglycan selectively inhibit identical smooth muscle cell populations. Similarly, these heparan sulfate enriched matrices lower smooth muscle sensitivity to heparin and positively influence the endothelial cells' ability to produce the heparin-like inhibitor of vascular smooth muscle cell growth. In an effort to understand the mechanism mediating heparin's effects on smooth muscle cell proliferation and contractile phenotype, we have analyzed the effects of heparin on vascular smooth muscle cell shape and actin isoform expression using doses of heparin previously shown to be growth inhibitory. The results of our studies indicate that heparin alters smooth muscle cell shape and cytoskeletal organization, suggesting that heparin's growth inhibitory action may be related to its effects on cell shape. Additionally, the permissive effects that different endothelial matrices exert on vascular smooth muscle may selectively predispose specific subpopulations of arterial cells towards a proliferating phenotype, one associated with the genesis of atherosclerosis.
尽管血管平滑肌细胞与细胞外基质的相互作用已得到深入研究，但我们对于基质在调节血管壁细胞生长状态和收缩表型中所起作用的了解仍不完整。特别值得关注的是：（1）肝素在体外选择性抑制血管平滑肌细胞生长的可证实能力；（2）主动脉内皮细胞产生血管平滑肌细胞的类肝素抑制剂；（3）肝素使实验性去除内皮的动脉中的平滑肌细胞增殖逆转。我们实验室最近的研究表明，内皮细胞合成的细胞外基质会改变血管平滑肌细胞的生长速率和对肝素的敏感性。含有胶原蛋白和纤连蛋白的内皮细胞合成基质可促进平滑肌细胞生长，而含有硫酸乙酰肝素蛋白聚糖的基质则选择性抑制相同的平滑肌细胞群体。同样，这些富含硫酸乙酰肝素的基质会降低平滑肌对肝素的敏感性，并积极影响内皮细胞产生血管平滑肌细胞生长类肝素抑制剂的能力。为了理解介导肝素对平滑肌细胞增殖和收缩表型作用的机制，我们使用先前已证明具有生长抑制作用的肝素剂量，分析了肝素对血管平滑肌细胞形态和肌动蛋白异构体表达的影响。我们的研究结果表明，肝素会改变平滑肌细胞形态和细胞骨架组织，提示肝素的生长抑制作用可能与其对细胞形态的影响有关。此外，不同内皮基质对血管平滑肌产生的允许作用可能会使动脉细胞的特定亚群选择性地倾向于增殖表型，这与动脉粥样硬化的发生有关。
