Effect of heparin on vascular smooth muscle cells. II. Specific protein synthesis.
Effect of heparin on vascular smooth muscle cells. II. Specific protein synthesis.
复制标题
肝素对血管平滑肌细胞的影响。
DOI：
10.1002/jcp.1041240106
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发表时间：
1985
影响因子：
5.6
通讯作者：
Karnovsky,MJ
中科院分区：
文献类型：
--
作者：
Cochran,DL;CastellotJr,JJ;Karnovsky,MJ
肝素在体内和体外均能抑制血管平滑肌细胞的增殖。肝素抗增殖活性的作用机制尚不清楚。我们已经检测到当血管平滑肌细胞暴露在肝素中时，特定蛋白质合成的差异，并在此报告这些蛋白质变化的许多特征与抗增殖活性的特性相似。在经肝素处理的血管细胞培养中，一对约35,000道尔顿分子量的蛋白质被诱导到培养液中，肝素的抗增殖作用具有如下特征：1)这种作用是可逆的，2)这种作用是针对平滑肌细胞的，3)抗凝剂和非抗凝剂肝素同样有效，4)这种作用随着培养时间的推移而消失，5)肝素对48,000道尔顿底物结合蛋白的瞬时抑制作用，而硫酸软骨素A、C和硫酸皮肤素的作用要小得多。在抑制底物结合蛋白的合成方面，硫酸葡聚糖几乎和肝素一样有效。这些蛋白似乎是非胶原蛋白，并且这些蛋白的诱导合成被放线菌素D抑制。虽然这些特定蛋白的变化与肝素的抗增殖作用之间的直接关系尚未得到证实，但这些蛋白的变化可能在肝素对平滑肌细胞生长的影响中起着至关重要的作用。
Heparin suppresses the proliferation of vascular smooth muscle cells both in vivo and in vitro. The mechanism of action of the antiproliferative activity of heparin is not known. We have detected differences in the synthesis of specific proteins when vascular smooth muscle cells are exposed to heparin and report here that many characteristics of these protein alterations parallel the properties of the antiproliferative activity. The induction into the culture medium of a pair of proteins of approximately 35,000 dalton mw in heparintreated smooth muscle cell cultures and the antiproliferative effect of heparin share the following characteristics: 1) the effect is reversible, 2) the effect is specific for smooth muscle cells, 3) anticoagulant and non‐anticoagulant heparin are equally effective, 4) the effect is lost with time in culture and, 5) thermore, heparin causes a transient suppression of a 48,000 dalton substrateattached protein, whereas chondroitin sulfate A and C and dermatan sulfate had much less effect. Dextran sulfate was almost as effective as heparin in suppressing the synthesis of the substrate‐attached protein. These proteins appear to be noncollagenous and the induced synthesis of the 35,000 dalton proteins is inhibited by actinomycin D. Although a direct relationship between these specific protein changes and the antiproliferative effect of heparin has not been proven, these protein alterations may play a crucial role in the effect of heparin on smooth muscle cell growth.