Giddings J C, Banning A P, Ralis H, Lewis M J
Department of Haematology, University of Wales College of Medicine, Cardiff, United Kingdom.
Arterioscler Thromb Vasc Biol. 1997 Oct;17(10):1872-8. doi: 10.1161/01.atv.17.10.1872.
von Willebrand factor (VWF) is a well-characterized multimeric glycoprotein present in platelets and plasma and synthesized by vascular endothelial cells and megakaryocytes. Its role in platelet-vessel wall interactions has been studied extensively, but its involvement in intravascular events after balloon angioplasty has not been clarified. VWF antigen is not present in porcine arterial endothelium (except for the pulmonary artery) but is readily detected in porcine venous endothelial cells. We have examined the localization of VWF in porcine vessel walls during neointima formation after bilateral carotid balloon-angioplasty. Endothelium was denuded by balloon injury but regenerated by 7 days and was fully confluent by 42 days. VWF was detected at the site of injury in localized, adherent platelet aggregates at 10 minutes after angioplasty that were not present at later time points. A well-demarcated homogeneous layer of VWF was observed on the luminal surface from 30 minutes to day 7, but there was a progressive shift of positive staining from the lumen to the outer media from days 1 to 7. VWF was also strongly detected at sites proximal and distal to the balloon injury from 30 minutes to day 7, although endothelial disruption was minimal and the monolayer remained substantially intact at these sites. Regrowing endothelial cells appeared to contain granular VWF from days 12 to 21, but this was not readily evident at later time points. The results suggest that balloon injury is associated with deposition and medial absorption of plasma or platelet VWF in this porcine model over a time period that precedes and overlaps vascular smooth muscle proliferation and endothelial recoverage. The findings provide evidence to support the concept of a wider role for VWF in tissue injury responses.
血管性血友病因子(VWF)是一种特征明确的多聚体糖蛋白,存在于血小板和血浆中,由血管内皮细胞和巨核细胞合成。其在血小板与血管壁相互作用中的作用已得到广泛研究,但在球囊血管成形术后血管内事件中的参与情况尚未明确。VWF抗原在猪动脉内皮(肺动脉除外)中不存在,但在猪静脉内皮细胞中很容易检测到。我们研究了双侧颈动脉球囊血管成形术后新生内膜形成过程中VWF在猪血管壁中的定位。内皮因球囊损伤而剥脱,但在7天时再生,42天时完全融合。血管成形术后10分钟,在损伤部位可检测到VWF存在于局部粘附的血小板聚集体中,后期则不存在。在30分钟至第7天,在管腔表面观察到一层界限清晰的均匀VWF层,但从第1天到第7天,阳性染色逐渐从管腔向中膜外层转移。在30分钟至第7天,在球囊损伤近端和远端部位也强烈检测到VWF,尽管内皮破坏最小且这些部位的单层基本保持完整。从第12天到第21天,再生的内皮细胞似乎含有颗粒状VWF,但在后期时间点不太明显。结果表明,在这个猪模型中,球囊损伤与血浆或血小板VWF在血管平滑肌增殖和内皮恢复之前及重叠的时间段内的沉积和中膜吸收有关。这些发现为支持VWF在组织损伤反应中具有更广泛作用的概念提供了证据。