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 diameter accordingly. The factors mediating this process are only beginning to be identified. We have recently established a mouse model of arterial remodeling in which flow in the common carotid artery is interrupted by ligation of the vessel near the carotid bifurcation, resulting in a dramatic reduction in vessel diameter as a consequence of inward remodeling and intimal lesion formation. In the present study, we used this model to determine the role of fibroblast growth factor-2 (FGF-7) in the remodeling response by maintaining neutralizing serum levels of a mouse monoclonal antibody against FGF-2 for 4 weeks. Morphometric analysis revealed that intimal lesion formation was not affected by the antibody. However, lumen narrowing was significantly inhibited, resulting in a greater than 3-fold increase in lumen area in anti-FGF-2-treated animals compared with controls. Treatment with anti-FGF-2 antibody significantly inhibited the reduction in vessel diameter (inward remodeling) and shortening of the internal elastic lamina in the ligated vessel. In addition, anti-FGF-2 treatment also caused outward remodeling of the contralateral carotid artery. These findings identify FGF-2 as an important factor in vascular remodeling, and its effects are likely to be mediated by increasing vascular tone. The results are consistent with the recent observation of reduced vascular tone in the FGF-2-deficient mouse.