EFFECT OF HEPARIN ON VASCULAR SMOOTH-MUSCLE CELLS .1. CELL-METABOLISM
EFFECT OF HEPARIN ON VASCULAR SMOOTH-MUSCLE CELLS .1. CELL-METABOLISM
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DOI：
10.1002/jcp.1041240105
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发表时间：
1985-01-01
影响因子：
5.6
通讯作者：
KARNOVSKY, MJ
中科院分区：
文献类型：
--
作者：
CASTELLOT, JJ;COCHRAN, DL;KARNOVSKY, MJ
肝素在体内外均能明显抑制血管平滑肌细胞的增殖。这种糖胺聚糖的作用机制尚不清楚。研究了肝素对平滑肌和其他细胞类型的抗增殖作用，以及肝素对平滑肌细胞代谢的几个方面。来自几个物种（包括人）的平滑肌和密切相关的细胞类型对肝素的敏感性远高于任何其他检测的细胞类型，包括原代和已建立的细胞系、正常和转化细胞对、成纤维细胞、上皮和内皮细胞。细胞周期分布的流式显微荧光分析表明肝素阻断了G 0 → G1/G2/G S期转变或平滑肌细胞中非常早期的S期事件。肝素迅速抑制DNA和RNA的合成，但不影响蛋白质的合成速率。核酸合成的减少可以通过抑制胸苷和尿苷摄取来解释。肝素不阻断氨基酸或葡萄糖转运。尽管在肝素存在下未观察到蛋白质合成的总体速率变化，但在平滑肌细胞合成特定蛋白质方面至少观察到2种变化：两种35，000-道尔顿蛋白质出现在肝素处理细胞的培养基中，以及48，000-道尔顿蛋白质在暴露于肝素的平滑肌细胞的底物附着材料中短暂消失。所观察到的平滑肌细胞代谢变化的作用尚未确定，但它们可能为控制肝素抗增殖活性的分子机制提供有价值的线索。
Heparin evidently inhibits the proliferation of vascular smooth muscle cells in vivo and in vitro. The mechanism of action of this glycosaminoglycan is unknown. The antiproliferative effect of heparin on smooth muscle and other cell types, and several aspects of heparin on smooth muscle cell metabolism were examined. Smooth muscle and closely related cell types from several species, including human, were much more sensitive to heparin than any other cell type tested, including primary and established cell lines, normal and transformed cell pairs, fibroblasts, epithelial and endothelial cells. Flow microfluorimetric analysis of cell cycle distribution indicated that heparin blocked either the G0 .fwdarw. S transition or a very early S-phase event in smooth muscle cells. Heparin rapidly inhibited DNA and RNA synthesis, but did not affect the rate of protein synthesis. Decrease in nucleic acid synthesis could be accounted for by an inhibition of thymidine and uridine uptake. Heparin did not block amino acid or glucose transport. Although no change in the overall rate of protein synthesis was observed in the presence of heparin, at least 2 changes were noted in the synthesis of specific proteins by smooth muscle cells: two 35,000-dalton proteins which appeared in the culture medium of heparin-treated cells, and the transient disappearance of a 48,000-dalton protein in the substrate attached material of smooth muscle cells exposed to heparin. The role of the observed changes in smooth muscle cell metabolism is yet to be determined, but they may provide valuable clues to the molecular mechanisms controlling the antiproliferative activity of heparin.