BASIC FIBROBLAST GROWTH-FACTOR ENHANCES THE COUPLING OF INTIMAL HYPERPLASIA AND PROLIFERATION OF VASA VASORUM IN INJURED RAT ARTERIES
BASIC FIBROBLAST GROWTH-FACTOR ENHANCES THE COUPLING OF INTIMAL HYPERPLASIA AND PROLIFERATION OF VASA VASORUM IN INJURED RAT ARTERIES
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DOI：
10.1172/jci115607
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发表时间：
1992-02-01
影响因子：
15.9
通讯作者：
KARNOVSKY, MJ
中科院分区：
文献类型：
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作者：
EDELMAN, ER;NUGENT, MA;KARNOVSKY, MJ
碱性成纤维细胞生长因子（bFGF）是平滑肌细胞（SMC）的促有丝分裂和血管生成因子。我们研究了bFGF在实验大鼠球囊剥脱颈动脉中的体内作用。bFGF从聚合物基装置以34 ng/d连续给药到大鼠颈动脉外膜周围空间2周。在无损伤或脂多糖诱导的内皮功能障碍的情况下未观察到内膜增生。不同程度的血管损伤均导致内膜增生。bFGF使严重血管损伤的内膜增生反应增加1.3倍，使较轻度损伤的内膜增生反应增加2.4倍。增加细胞增殖，而不是细胞外基质的生产，占这些影响。对照组和bFGF治疗组的细胞密度无变化，2周时增殖内膜细胞的数量上升至相当于质量增加的数量;严重损伤和轻度损伤分别为1.9倍和4.0倍。肝素降低SMC增殖的相对能力并没有因为bFGF的存在而改变。bFGF还诱导了聚合物释放装置内和周围以及紧邻损伤动脉周围的血管中的深刻的血管生成。bFGF对血管的影响与血管内SMC增殖量呈线性相关。因此，bFGF的体内促有丝分裂和血管生成潜力是偶联的，并且可以类似地由局部损伤的产物和/或血管壁中的因子调节。
Basic fibroblast growth factor (bFGF) is mitogenic for smooth muscle cells (SMC) and angiogenic. We examined the in vivo effects of bFGF in balloon denuded carotid arteries of laboratory rats. bFGF was administered continuously from polymerbased devices at 34 ng/d into the periadventitial space of rat carotid arteries for 2 wk. Intimal hyperplasia was not observed in the absence of injury or with lipopolysaccharide induced endothelial dysfunction. Different degrees of vascular injury produced proportionally more intimal hyperplasia. bFGF increased the intimal hyperplastic response 1.3-fold with severe vascular injury, and 2.4-fold with more mild injury. Increased cell proliferation, not extracellular matrix production, accounted for these effects. Cell density was unchanged for the control and bFGF-treated groups, and the number of proliferating intimal cells at 2 wk rose to an amount equivalent to the increase in mass; 1.9- and 4.0-fold for severe and lesser injury, respectively. The relative ability of heparin to reduce SMC proliferation was not altered by the presence of bFGF. bFGF also induced profound angiogenesis within and surrounding the polymeric releasing device, and in the vasa vasorum immediately around the injured arteries. bFGF's effect on vasa was linearly related to the amount of SMC proliferation within the blood vessel. Thus, the in vivo mitogenic and angiogenic potential of bFGF are coupled, and may be similarly modulated by the products of local injury and/or factors in the vessel wall.