Savani R C, Turley E A
Department of Pediatrics, University of Manitoba, Winnipeg, Canada.
Int J Tissue React. 1995;17(4):141-51.
Atherosclerosis is a progressive condition that is initiated by endothelial injury, promoted by growth factors, and which results in the formation of fibrofatty plaques that narrow the affected blood vessel. Balloon angioplasty is used to dilate these plaques in the coronary circulation so as to prevent occlusion of this critical blood supply. However, 30-50% of balloon dilatations end in restenosis within six months of the procedure. The pathogenesis of both atherosclerosis and restenosis after balloon angioplasty involves the migration of medial smooth-muscle cells across the internal elastic lamina to form a neointima. Proliferation of these cells and their elaboration of an extracellular matrix results in stenosis of the affected area. Investigation of several animal models, as well as of the human condition, indicates the presence of an ongoing inflammatory reaction involving T cells and other leukocytes which probably maintain smooth-muscle cell migration, proliferation and matrix deposition. We have shown that the stenotic response involves the expression of HA (hyaluronan) receptors on both the infiltrating white cells and on smooth-muscle cell populations. Thus, in vitro, the locomotion and chemotaxis of these cells in response to injury is inhibited by reagents that block HA-receptor interactions including HA-binding peptides and high doses of HA. Further, the expression of these HA receptors is up-regulated after balloon-catheter injury of the rat carotid artery, and exposure of injured arteries to high concentrations of HA in vivo results in significant inhibition of neointimal formation. The possible clinical benefits of this response are discussed.
动脉粥样硬化是一种渐进性疾病，由内皮损伤引发，生长因子促进其发展，并导致纤维脂肪斑块形成，使受影响的血管变窄。球囊血管成形术用于扩张冠状动脉循环中的这些斑块，以防止这一关键血液供应的阻塞。然而，30%至50%的球囊扩张术在术后六个月内以再狭窄告终。动脉粥样硬化和球囊血管成形术后再狭窄的发病机制都涉及中膜平滑肌细胞穿过内弹性膜迁移以形成新内膜。这些细胞的增殖及其细胞外基质的形成导致受影响区域的狭窄。对几种动物模型以及人类疾病状况的研究表明，存在涉及T细胞和其他白细胞的持续炎症反应，这可能维持平滑肌细胞的迁移、增殖和基质沉积。我们已经表明，狭窄反应涉及浸润白细胞和平滑肌细胞群体上透明质酸（HA）受体的表达。因此，在体外，这些细胞对损伤的运动和趋化作用受到阻断HA受体相互作用的试剂的抑制，这些试剂包括HA结合肽和高剂量的HA。此外，大鼠颈动脉球囊导管损伤后，这些HA受体的表达上调，并且在体内将损伤动脉暴露于高浓度的HA会导致新内膜形成的显著抑制。本文讨论了这种反应可能的临床益处。
