ANTIBODIES AGAINST TRANSFORMING GROWTH-FACTOR-BETA-1 SUPPRESS INTIMAL HYPERPLASIA IN A RAT MODEL
ANTIBODIES AGAINST TRANSFORMING GROWTH-FACTOR-BETA-1 SUPPRESS INTIMAL HYPERPLASIA IN A RAT MODEL
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DOI：
10.1172/jci117070
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发表时间：
1994-03-01
影响因子：
15.9
通讯作者：
RUOSLAHTI, E
中科院分区：
文献类型：
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作者：
WOLF, YG;RASMUSSEN, LM;RUOSLAHTI, E
内膜增生是由治疗性血管干预引起的，通常会导致临床上重要的血管腔狭窄。对大鼠颈动脉损伤模型中 TGF-β1 作用的检查证实了先前报道的受损动脉中膜中 TGF-β1 mRNA 的增加。施用中和性抗 TGF-β1 抗体可显着 (P < 0.05) 减少颈动脉球囊损伤后形成的内膜损伤的大小。对照抗体没有效果。相对于对照组，抗 TGF-β1 组的内膜/内侧面积比也有所降低（P < 0.01）。免疫组织化学染色显示，两种TGF-β1诱导的细胞外基质成分EDA+纤连蛋白和多功能蛋白聚糖在未治疗的新内膜病变中显着增加，但在抗TGF-β1治疗的动物的病变中几乎完全不存在。我们得出的结论是，TGF-β1 与内膜增生的发展有因果关系，并且抗 TGF-β1 药物可能有助于至少部分控制这种情况。
Intimal hyperplasia is induced by therapeutic vascular interventions and often results in clinically important narrowing of the vascular lumen. Examination of the role of TGF-beta 1 in a rat carotid artery injury model confirmed the presence of a previously reported increase in TGF-beta 1 mRNA in the media of injured arteries. Administration of neutralizing anti-TGF-beta 1 antibodies significantly (P < 0.05) reduced the size of the intimal lesions that developed after carotid balloon injury. A control antibody had no effect. The intimal/medial area ratio was also reduced in the anti-TGF-beta 1 group relative to controls (P < 0.01). Immunohistochemical staining showed that two TGF-beta 1-induced extracellular matrix components, EDA+ fibronectin and versican, were greatly increased in the untreated neointimal lesions, but were almost completely absent from the lesions of the anti-TGF-beta 1-treated animals. We conclude that TGF-beta 1 is causally involved in the development of intimal hyperplasia, and that anti-TGF-beta 1 agents may be useful in achieving at least partial control of this condition.