Vascular remodeling in response to altered blood flow is mediated by fibroblast growth factor-2

Vascular structures adapt to changes in blood flow by adjusting their diame ter accordingly. The factors mediating this process are only beginning to b e identified. We have recently established a mouse model of arterial remode ling in which flow in the common carotid artery is interrupted by ligation of the vessel near the carotid bifurcation, resulting in a dramatic reducti on in vessel diameter as a consequence of inward remodeling and intimal les ion formation. In the present study, we used this model to determine the ro le of fibroblast growth factor-2 (FGF-7) in the remodeling response by main taining neutralizing serum levels of a mouse monoclonal antibody against FG F-2 for 4 weeks. Morphometric analysis revealed that intimal lesion formati on was not affected by the antibody. However, lumen narrowing was significa ntly inhibited, resulting in a greater than 3-fold increase in lumen area i n anti-FGF-2-treated animals compared with controls. Treatment with anti-FG F-2 antibody significantly inhibited the reduction in vessel diameter (inwa rd remodeling) and shortening of the internal elastic lamina in the ligated vessel. In addition, anti-FGF-2 treatment also caused outward remodeling o f the contralateral carotid artery. These findings identify FGF-2 as an imp ortant factor in vascular remodeling, and its effects are likely to be medi ated by increasing vascular tone. The results are consistent with the recen t observation of reduced vascular tone in the FGF-2-deficient mouse.