Winkles J A, Friesel R, Burgess W H, Howk R, Mehlman T, Weinstein R, Maciag T
Biotechnology Research Center, Meloy Laboratories, Inc., Rockville, MD 20850.
Proc Natl Acad Sci U S A. 1987 Oct;84(20):7124-8. doi: 10.1073/pnas.84.20.7124.
The control of vascular endothelial and smooth muscle cell proliferation is important in such processes as tumor angiogenesis, wound healing, and the pathogenesis of atherosclerosis. Class I heparin-binding growth factor (HBGF-I) is a potent mitogen and chemoattractant for human endothelial cells in vitro and will induce angiogenesis in vivo. RNA gel blot hybridization experiments demonstrate that cultured human vascular smooth muscle cells, but not human umbilical vein endothelial cells, express HBGF-I mRNA. Smooth muscle cells also synthesize an HBGF-I-like polypeptide since (i) extract prepared from smooth muscle cells will compete with 125I-labeled HBGF-I for binding to the HBGF-I cell surface receptor, and (ii) the competing ligand is eluted from heparin-Sepharose affinity resin at a NaCl concentration similar to that required by purified bovine brain HBGF-I and stimulates endothelial cell proliferation in vitro. Furthermore, like endothelial cells, smooth muscle cells possess cell-surface-associated HBGF-I receptors and respond to HBGF-I as a mitogen. These results indicate the potential for an additional autocrine component of vascular smooth muscle cell growth control and establish a vessel wall source of HBGF-I for endothelial cell division in vivo.
血管内皮细胞和平滑肌细胞增殖的调控在肿瘤血管生成、伤口愈合以及动脉粥样硬化的发病机制等过程中具有重要意义。I类肝素结合生长因子（HBGF-I）在体外是一种对人内皮细胞有强大作用的促有丝分裂原和趋化因子，并且在体内能诱导血管生成。RNA凝胶印迹杂交实验表明，培养的人血管平滑肌细胞而非人脐静脉内皮细胞表达HBGF-I mRNA。平滑肌细胞还能合成一种类似HBGF-I的多肽，原因如下：（i）从平滑肌细胞制备的提取物能与125I标记的HBGF-I竞争结合HBGF-I细胞表面受体；（ii）竞争配体从肝素-琼脂糖亲和树脂上洗脱时所需的NaCl浓度与纯化的牛脑HBGF-I所需浓度相似，且能在体外刺激内皮细胞增殖。此外，与内皮细胞一样，平滑肌细胞也拥有与细胞表面相关的HBGF-I受体，并对HBGF-I作为促有丝分裂原产生反应。这些结果表明血管平滑肌细胞生长调控可能存在额外的自分泌成分，并确定了体内血管壁为内皮细胞分裂提供HBGF-I的来源。
