Fingerle J, Johnson R, Clowes A W, Majesky M W, Reidy M A
Department of Pathology, University of Washington, Seattle 98195.
Proc Natl Acad Sci U S A. 1989 Nov;86(21):8412-6. doi: 10.1073/pnas.86.21.8412.
Intimal lesion formation was investigated in rats made thrombocytopenic by a single i.p. injection of a polyclonal antibody made against rat platelets that reduced circulating platelet counts to less than 1% of normal. The carotid artery was then denuded of endothelium with a 2 French balloon catheter, after which no platelets were found adhering to the exposed subendothelium. In control animals, platelets adhered instantly to the denuded artery. Six hours after denudation mRNA for ornithine decarboxylase, a marker for early G1 events, was found to be elevated in both thrombocytopenic and control arteries. Two days after injury the smooth muscle cell replication rate in thrombocytopenic rats was found to be significantly elevated as compared with that in uninjured carotids (13.7% +/- 8.4% vs. 0.65% +/- 0.23%) but was similar to the replication rate observed in denuded carotid arteries from animals treated with nonimmune IgG. One important difference between these animals was that no intimal thickening was observed in thrombocytopenic animals at day 4, and by day 7 the intimas were still significantly smaller than those from control rats. In a separate group of animals which were thrombocytopenic for the entire experiment, no intimal lesions were observed 7 days after injury by balloon catheter. From these results, we conclude that platelets do not play a role in the initiation of smooth muscle cell proliferation after injury by balloon catheter but may regulate their movement into the intima.
通过腹腔注射针对大鼠血小板的多克隆抗体使大鼠血小板减少，将循环血小板计数降至正常水平的1%以下，以此研究内膜损伤的形成。然后用2F球囊导管剥脱颈动脉内皮，之后未发现血小板黏附于暴露的内皮下层。在对照动物中，血小板立即黏附于剥脱的动脉。剥脱后6小时，在血小板减少的动脉和对照动脉中均发现鸟氨酸脱羧酶（早期G1期事件的标志物）的mRNA水平升高。损伤后两天，发现血小板减少大鼠的平滑肌细胞复制率与未损伤的颈动脉相比显著升高（13.7%±8.4%对0.65%±0.23%），但与用非免疫IgG处理的动物的剥脱颈动脉中观察到的复制率相似。这些动物之间的一个重要差异是，在第4天血小板减少的动物中未观察到内膜增厚，到第7天，内膜仍明显小于对照大鼠的内膜。在另一组整个实验过程中血小板减少的动物中，球囊导管损伤后7天未观察到内膜损伤。从这些结果中，我们得出结论，血小板在球囊导管损伤后平滑肌细胞增殖的起始过程中不起作用，但可能调节它们向内膜的移动。
