BASIC FIBROBLAST-GROWTH-FACTOR EXPRESSION PRECEDES FLOW-INDUCED ARTERIAL ENLARGEMENT

Arteries enlarge in response to increased blood now, but the molecular signals controlling this enlargement are not well understood. Basic f ibroblast growth factor (bFGF) is a potent mitogen for endothelial cel ls (EC) and smooth muscle cells (SMC) and promotes cellular proliferat ion and differentiation. In order to determine whether bFGF is express ed in response to increased blood Bow in vivo carotid-jugular arteriov enous fistulas (AVF) were created in Japanese white rabbits. The carot id artery proximal to the fistula was harvested after 1, 3, or 7 days and compared to nonoperated, control carotid arteries. Arterial blood Bow 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. Immun ohistochemical analysis revealed bFGF protein localization in EC of co ntrol arteries as well as AVF arteries at all time points, SMC and adv entitia expression of bFGF was absent in controls, minimal at 1 day, a nd increased after 3 and 7 days in the experimental groups. Western bl otting confirmed the presence of bFGF in samples and transmission immu noelectron microscopy confirmed its nuclear localization. Endothelial cells in vivo express bFGF under both normal and elevated Bow conditio ns. Smooth muscle cells, however, do not express bFGF under normal Bow conditions but begin to express bFGF after 1 day of high Bow with inc reased expression after 3 and 7 days. Flow-induced arterial enlargemen t begins after SMC expression of bFGF, Therefore, bFGF may play a role in arterial enlargement and adaptive remodeling in response to increa sed flow. (C) 1998 Academic Press.