Singh T M, Abe K Y, Sasaki T, Zhuang Y J, Masuda H, Zarins C K
Department of Vascular Surgery, Stanford University, Stanford, California, 94305, USA.
J Surg Res. 1998 Jul 1;77(2):165-73. doi: 10.1006/jsre.1998.5376.
Arteries enlarge in response to increased blood flow, but the molecular signals controlling this enlargement are not well understood. Basic fibroblast growth factor (bFGF) is a potent mitogen for endothelial cells (EC) and smooth muscle cells (SMC) and promotes cellular proliferation and differentiation. In order to determine whether bFGF is expressed in response to increased blood flow in vivo, carotid-jugular arteriovenous fistulas (AVF) were created in Japanese white rabbits. The carotid artery proximal to the fistula was harvested after 1, 3, or 7 days and compared to nonoperated, control carotid arteries. Arterial blood flow increased five- to eightfold in all AVF animals and resulted in a significant increase in wall shear stress. The proximal carotid artery arterial diameter was no different from control after 1 and 3 days (2.3 +/- 0. 1 mm) but enlarged to 2.9 +/- 0.1 mm (P < 0.05) after 7 days. RT-PCR revealed early transcription of bFGF mRNA at 1 and 3 days with increased densitometric band ratio (bFGF/beta-actin) at 7 days. Immunohistochemical analysis revealed bFGF protein localization in EC of control arteries as well as AVF arteries at all time points. SMC and adventitia expression of bFGF was absent in controls, minimal at 1 day, and increased after 3 and 7 days in the experimental groups. Western blotting confirmed the presence of bFGF in samples and transmission immunoelectron microscopy confirmed its nuclear localization. Endothelial cells in vivo express bFGF under both normal and elevated flow conditions. Smooth muscle cells, however, do not express bFGF under normal flow conditions but begin to express bFGF after 1 day of high flow with increased expression after 3 and 7 days. Flow-induced arterial enlargement begins after SMC expression of bFGF. Therefore, bFGF may play a role in arterial enlargement and adaptive remodeling in response to increased flow.
动脉会因血流量增加而扩张，但其控制这种扩张的分子信号尚未完全明确。碱性成纤维细胞生长因子（bFGF）是一种对内皮细胞（EC）和平滑肌细胞（SMC）有效的促有丝分裂原，可促进细胞增殖和分化。为了确定bFGF在体内是否因血流量增加而表达，在日本白兔身上建立了颈静脉动静脉瘘（AVF）。在术后1、3或7天采集瘘口近端的颈动脉，并与未手术的对照颈动脉进行比较。所有AVF动物的动脉血流量增加了5至8倍，导致壁切应力显著增加。术后1天和3天，近端颈动脉直径与对照组无差异（2.3±0.1mm），但术后7天扩大至2.9±0.1mm（P<0.05）。逆转录聚合酶链反应（RT-PCR）显示，术后1天和3天bFGF mRNA早期转录，术后7天光密度带比（bFGF/β-肌动蛋白）增加。免疫组织化学分析显示，在所有时间点，bFGF蛋白均定位于对照动脉和AVF动脉的内皮细胞中。对照组中SMC和外膜无bFGF表达，术后1天表达极少，实验组术后3天和7天表达增加。蛋白质印迹法证实样本中存在bFGF，透射免疫电子显微镜证实其定位于细胞核。体内内皮细胞在正常和高流量条件下均表达bFGF。然而，平滑肌细胞在正常流量条件下不表达bFGF，但在高流量1天后开始表达bFGF，术后3天和7天表达增加。SMC表达bFGF后开始出现血流诱导的动脉扩张。因此，bFGF可能在动脉扩张和对血流增加的适应性重塑中发挥作用。
