Spears J R, Zhan H, Khurana S, Karvonen R L, Reiser K M
Department of Medicine, Harper Hospital/Wayne State University School of Medicine, Detroit, Michigan 48201.
J Clin Invest. 1994 Apr;93(4):1543-53. doi: 10.1172/JCI117133.
This study was designed to assess the potential relationship between the late loss of angiographic luminal diameter and biochemical abnormalities of arterial wall collagen in rabbits subjected to angioplasty, and to test the hypothesis that beta-aminopropionitrile (beta APN), an inhibitor of lysyl oxidase, would inhibit such changes when administered orally for 1 mo after angioplasty. Endovascular injury was induced in rabbit iliac arteries by ipsilateral balloon angioplasty (BA) and by contralateral balloon angioplasty accompanied by exposure to continuous wave neodymium: yttrium aluminum garnet laser radiation (LBA). Computer measurement of angiographic luminal diameter demonstrated significant vessel narrowing at 1 and 6 mo after both procedures. By quantitative histology, the majority of the 1-mo loss in angiographic diameter could not be attributed to neointimal thickening. Analysis of collagen cross-linking by HPLC in collagen obtained from the LBA-injured segments of the arteries 1 mo after angioplasty revealed a significant increase, relative to values from uninjured arteries (P < 0.05), in the difunctional cross-link dihydroxylysinonorleucine (DHLNL). 6 mo after angioplasty, the content of hydroxypyridinium, the trifunctional maturational product of DHLNL, was significantly elevated in both BA- and LBA-treated arteries compared with values from uninjured arteries (P < 0.05). In animals administered beta APN, luminal narrowing at 1 mo, compared with controls, was attenuated (P < 0.01) and DHLNL content was decreased (P < 0.05) in arteries subjected to LBA, but not in arteries subjected to BA. The results suggest that lathyrogenic agents may be efficacious in favorably modulating LBA-induced alterations in vessel diameter and mural connective tissue.
本研究旨在评估血管成形术后兔血管造影管腔直径晚期丢失与动脉壁胶原生化异常之间的潜在关系,并检验以下假设:赖氨酰氧化酶抑制剂β-氨基丙腈(βAPN)在血管成形术后口服1个月可抑制此类变化。通过同侧球囊血管成形术(BA)和对侧球囊血管成形术并同时暴露于连续波钕:钇铝石榴石激光辐射(LBA)诱导兔髂动脉血管内损伤。计算机测量血管造影管腔直径显示,两种手术后1个月和6个月时血管均出现明显狭窄。通过定量组织学分析,血管造影直径1个月时的大部分丢失不能归因于新生内膜增厚。血管成形术后1个月,对LBA损伤动脉段获取的胶原进行HPLC分析胶原交联,结果显示,与未损伤动脉的值相比,双功能交联二羟基赖氨酰正亮氨酸(DHLNL)显著增加(P<0.05)。血管成形术后6个月,与未损伤动脉的值相比,BA和LBA治疗的动脉中DHLNL的三功能成熟产物羟基吡啶鎓的含量均显著升高(P<0.05)。在给予βAPN的动物中,与对照组相比,LBA处理的动脉1个月时管腔狭窄减轻(P<0.01),DHLNL含量降低(P<0.05),但BA处理的动脉未出现此情况。结果表明,致纤维化剂可能有效调节LBA诱导的血管直径和血管壁结缔组织改变。