Lindner V, Reidy M A
Department of Pathology, University of Washington, Seattle 98195.
Circ Res. 1993 Sep;73(3):589-95. doi: 10.1161/01.res.73.3.589.
Release of endogenous basic fibroblast growth factor (bFGF) has been shown to initiate smooth muscle cell (SMC) proliferation following balloon catheter denudation in rat arteries. The mechanisms that contribute to the continued replication of the cells that subsequently form the neointima are not well understood. We have examined expression of bFGF and fibroblast growth factor receptor 1 (FGFR-1) in luminal SMCs as well as endothelium at various times after injury, which allowed us to study both replicating as well as quiescent cells. Using in situ hybridization on en face preparations, we were able to detect mRNA in luminal cells that was not observed by analysis of artery cross sections. We demonstrate that mRNA for bFGF was found in replicating SMCs and endothelial cells. bFGF mRNA was not detectable in either cell type at quiescence despite nuclear staining for bFGF. Expression of FGFR-1 mRNA was observed in replicating endothelial and SMCs at similar times after injury. These data provide evidence that in injured arteries the ligand/receptor system of bFGF and FGFR-1 may be involved in the continued proliferative response of SMCs leading to neointima formation. Furthermore, our results suggest a role for bFGF in reestablishing the endothelial lining in denuded vessels.
内源性碱性成纤维细胞生长因子(bFGF)的释放已被证明在大鼠动脉球囊导管剥脱后可引发平滑肌细胞(SMC)增殖。然而,对于随后形成新生内膜的细胞持续复制的机制,目前尚不清楚。我们研究了损伤后不同时间点管腔SMC以及内皮细胞中bFGF和成纤维细胞生长因子受体1(FGFR-1)的表达情况,这使我们能够同时研究正在复制的细胞和静止细胞。通过对血管表面标本进行原位杂交,我们能够检测到在动脉横断面分析中未观察到的管腔细胞中的mRNA。我们证明,在正在复制的SMC和内皮细胞中发现了bFGF的mRNA。尽管bFGF呈核染色,但在静止状态下两种细胞类型中均未检测到bFGF mRNA。在损伤后相似的时间,在正在复制的内皮细胞和SMC中观察到FGFR-1 mRNA的表达。这些数据提供了证据,表明在损伤的动脉中,bFGF和FGFR-1的配体/受体系统可能参与了导致新生内膜形成的SMC持续增殖反应。此外,我们的结果表明bFGF在裸露血管内皮衬里的重建中发挥作用。