Heparin and the phenotype of adult human vascular smooth muscle cells.
Heparin and the phenotype of adult human vascular smooth muscle cells.
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肝素和成人血管平滑肌细胞的表型。
DOI：
10.1007/bf02634088
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发表时间：
1995
期刊：
影响因子：
--
通讯作者：
Levine,EM
中科院分区：
文献类型：
--
作者：
Sorger,T;Friday,N;Yang,LD;Levine,EM
为了研究人类血管平滑肌细胞生长和表型的控制机制，我们建立了平滑肌细胞快速增殖和寿命达到50-60倍的培养条件。在含有肝素和肝素结合生长因子的培养基中，人血管平滑肌细胞的生长速度和寿命比不添加肝素和肝素结合生长因子的培养物增加50%以上，比只添加肝素结合生长因子的培养物增加20%以上。与在大鼠血管平滑肌细胞中的观察结果相反，人类平滑肌细胞中的α-肌动蛋白仅在肝素存在的情况下表达，并与应激纤维中的β/γ非肌肉肌动蛋白共定位，而不是在粘附斑块中。在肝素结合生长因子存在的情况下，肝素也引起示踪剂葡萄糖胺掺入透明质酸的刺激超过170%，透明质酸积累增加7.5倍。相比之下，硫酸化糖胺聚糖的总硫酸盐掺入量增加了不到40%。根据我们之前的研究结果，肝素抑制胶原基因表达，我们得出结论，肝素通过改变透明质酸（HA）和胶原合成的相对速率，诱导暴露于肝素结合生长因子的人血管平滑肌细胞重塑其细胞外基质。由此产生的富含透明质酸、缺乏胶原的基质可能会增强携带CD44/透明质酸受体的t淋巴细胞和单核细胞向血管壁的浸润，这是动脉粥样硬化的早期事件。
To study mechanisms controlling growth and phenotype in human vascular smooth muscle cells, we established culture conditions under which these cells proliferate rapidly and achieve life-spans of 50–60 population doublings. In medium containing heparin and heparin-binding growth factors, growth rate and life-span of human vascular smooth muscle cells increased more than 50% relative to cultures with neither supplement, and more than 20% compared to cultures supplemented only with heparin-binding growth factors. In contrast to observations made in rat vascular smooth muscle cells, smooth muscle-specific α-actin in the human cells was expressed only in the presence of heparin and colocalized with β/γ nonmuscle actins in stress fibers, not in adhesion plaques. Heparin, in the presence of heparin-binding growth factors, also caused more than 170% stimulation of tracer glucosamine incorporation into hyaluronic acid and a 7.5-fold increase in hyaluronic acid accumulation. In comparison, total sulfate incorporation into sulfated glycosaminoglycans increased by less than 40%. In light of our previous findings that heparin suppresses collagen gene expression, we conclude that heparin induces human vascular smooth muscle cells exposed to heparin-binding growth factors to remodel their extracellular matrix by altering the relative rates of hyaluronic acid (HA) and collagen synthesis. The resulting hyaluronic-acid-rich, collagen-poor matrix may enhance infiltration of CD44/hyaluronate-receptor-bearing T-lymphocytes and monocytes into the vascular wall, an early event in atherogenesis.