West J L, Hubbell J A
Department of Biomedical Engineering, University of Texas, Austin 78712, USA.
Proc Natl Acad Sci U S A. 1996 Nov 12;93(23):13188-93. doi: 10.1073/pnas.93.23.13188.
The objective of this study was to clarify the relative roles of medial versus luminal factors in the induction of thickening of the arterial intima after balloon angioplasty injury. Platelet-derived growth factor (PDGF) and thrombin, both associated with thrombosis, and basic fibroblast growth factor (bFGF), stored in the arterial wall, have been implicated in this process. To unequivocally isolate the media from luminally derived factors, we used a 20-microns thick hydrogel barrier that adhered firmly to the arterial wall to block thrombus deposition after balloon-induced injury of the carotid artery of the rat. Thrombosis, bFGF mobilization, medial repopulation, and intimal thickening were measured. Blockade of postinjury arterial contact with blood prevented thrombosis and dramatically inhibited both intimal thickening and endogenous bFGF mobilization. By blocking blood contact on the two time scales of thrombosis and of intimal thickening, and by using local protein release to probe, by reconstitution, the individual roles of PDGF-BB and thrombin, we were able to conclude that a luminally derived factor other than PDGF or thrombin is required for the initiation of cellular events leading to intimal thickening after balloon injury in the rat. We further conclude that a luminally derived factor is required for mobilization of medial bFGF.
本研究的目的是阐明在球囊血管成形术损伤后动脉内膜增厚诱导过程中，中层因素与腔内因素的相对作用。与血栓形成相关的血小板衍生生长因子（PDGF）和凝血酶，以及储存在动脉壁中的碱性成纤维细胞生长因子（bFGF），均与这一过程有关。为了明确地将中层与腔内来源的因素区分开，我们使用了一种20微米厚的水凝胶屏障，它能牢固地粘附在动脉壁上，以阻止大鼠颈动脉球囊损伤后血栓的沉积。我们对血栓形成、bFGF动员、中层再填充和内膜增厚进行了测量。损伤后动脉与血液的接触被阻断可防止血栓形成，并显著抑制内膜增厚和内源性bFGF的动员。通过在血栓形成和内膜增厚的两个时间尺度上阻断血液接触，并利用局部蛋白质释放通过重组来探究PDGF-BB和凝血酶的各自作用，我们能够得出结论，在大鼠球囊损伤后，导致内膜增厚的细胞事件启动需要一种除PDGF或凝血酶之外的腔内来源因子。我们进一步得出结论，中层bFGF的动员需要一种腔内来源因子。
