INHIBITION OF SMOOTH-MUSCLE CELL-PROLIFERATION IN INJURED RAT ARTERIES - INTERACTION OF HEPARIN WITH BASIC FIBROBLAST GROWTH-FACTOR
INHIBITION OF SMOOTH-MUSCLE CELL-PROLIFERATION IN INJURED RAT ARTERIES - INTERACTION OF HEPARIN WITH BASIC FIBROBLAST GROWTH-FACTOR
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DOI：
10.1172/jci116085
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发表时间：
1992-11-01
影响因子：
15.9
通讯作者：
REIDY, MA
中科院分区：
文献类型：
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作者：
LINDNER, V;OLSON, NE;REIDY, MA
肝素通过尚未明确的机制抑制动脉损伤后平滑肌细胞 (SMC) 的增殖。由于 SMC 增殖的启动是由碱性成纤维细胞生长因子 (bFGF) 介导的，因此我们研究了肝素通过取代动脉壁上的 bFGF 来抑制 SMC 增殖的可能性。使用球囊导管损伤的大鼠颈动脉模型，我们证明推注肝素会消耗动脉壁中全身施用的 bFGF 和内源性 bFGF。然而，肝素不会降低未操作动脉的 bFGF 含量。此外，球囊损伤时单次注射肝素可使 SMC 增殖减少 55%，但损伤后 6 小时注射则没有效果。通过注射 bFGF 在裸露动脉中诱导的 SMC 增殖几乎被肝素推注完全抑制；然而，用肝素推注进行预处理并不能阻止 SMC 对随后的 bFGF 推注做出反应。这些实验表明，肝素可以部分通过去除损伤部位释放的 bFGF 来抑制 SMC 增殖。
Heparin inhibits smooth muscle cell (SMC) proliferation after arterial injury by mechanisms that have yet to be defined. Since the initiation of SMC proliferation is mediated by basic fibroblast growth factor (bFGF), we have investigated the possibility that heparin inhibits SMC proliferation by displacing bFGF from the arterial wall. Using a rat carotid artery model of balloon catheter injury, we demonstrate that a bolus injection of heparin depletes the arterial wall of both systemically administered bFGF and of endogenous bFGF. Heparin, however, does not reduce the bFGF content of unmanipulated arteries. Further, a single injection of heparin given at the time of balloon injury reduces SMC proliferation by 55% but has no effect when given 6 h after injury. SMC proliferation induced in a denuded artery by injection of bFGF is inhibited almost completely by a bolus injection of heparin; however, pretreatment with a bolus of heparin does not prevent SMC from responding to a subsequent bolus of bFGF. These experiments suggest that heparin can inhibit SMC proliferation in part by removal of released bFGF from sites of injury.