Koyama H, Reidy M A
Department of Pathology, University of Washington, Seattle 98195-7335, USA.
Circ Res. 1997 Mar;80(3):408-17.
In this study we have examined the response of rat carotid arteries with intimal lesions to an angioplasty injury. Rat carotid arteries were subjected to injury with a 2F Fogarty catheter (first injury), and 28 days later the same arteries were subjected to reinjury with a 1.5-mm-diameter coronary dilation catheter (second injury) or a sham operation. After the second injury, the injured arterial surfaces were covered by a platelet monolayer, with occasional small thrombi. The size of the intimal area was significantly increased 28 days after the second injury, although the luminal area was not changed at this time. Intimal and medial cell replication, measured by 5-bromo-2'-deoxyuridine labeling, was significantly increased at 2 days after the second injury but was markedly reduced by 7 days. Addition of fibroblast growth factor-2 (FGF2, 60 micrograms i.v.) did not increase smooth muscle cell (SMC) replication in arteries subjected to the second injury, and replication was not inhibited with an antibody against FGF2 (120 mg i.v.). Both these reagents, however, did significantly affect SMC replication in normal carotid arteries subjected to Fogarty catheter injury. In a similar manner, heparin (888 UPS units/kg body wt i.v.) did not inhibit cell replication after second injury, although it did suppress SMC replication after a single injury. One conclusion is that rat intimal cells in vivo are different from medial SMCs and that other, as-yet-unknown, factors are important for their proliferation.
在本研究中,我们检测了患有内膜损伤的大鼠颈动脉对血管成形术损伤的反应。用2F Fogarty导管对大鼠颈动脉造成损伤(首次损伤),28天后,用直径1.5毫米的冠状动脉扩张导管对同一动脉再次造成损伤(二次损伤)或进行假手术。二次损伤后,损伤的动脉表面覆盖有血小板单层,偶尔有小血栓。二次损伤28天后,内膜面积显著增加,尽管此时管腔面积未改变。通过5-溴-2'-脱氧尿苷标记测量,内膜和中膜细胞复制在二次损伤后2天显著增加,但在7天时明显减少。添加成纤维细胞生长因子-2(FGF2,静脉注射60微克)并未增加遭受二次损伤的动脉中平滑肌细胞(SMC)的复制,并且用抗FGF2抗体(静脉注射120毫克)也未抑制复制。然而,这两种试剂确实显著影响了遭受Fogarty导管损伤的正常颈动脉中的SMC复制。同样,肝素(静脉注射888单位/千克体重)在二次损伤后并未抑制细胞复制,尽管它在单次损伤后确实抑制了SMC复制。一个结论是,体内大鼠内膜细胞与中膜SMC不同,并且其他尚未知晓的因素对它们的增殖很重要。