Protective effects of basic fibroblast growth factor in early atherosclerosis

Objectives: The role of basic fibroblast growth factor (bFGF) in atherosclerotic plaque formation is incompletely understood. Although it may act as a proatherogenic factor due to its stimulatory effect on smooth muscle cell growth, previous studies have suggested that it may also have beneficial effects by reversing endothelial dysfunction in experimental models. Our purpose was to evaluate the effects of systemic chronic administration of basic FGF on the development of atherosclerotic plaques in a rabbit model. Method: We investigated the effect of bFGF or placebo (2.5 mug IV twice a week), begun on the same day as a cholesterol (2%) diet, and continued for 5 or 10 weeks, on in vitro reactivity, vascular cell adhesion molecule-1 (VCAM-1) expression and plaque development (protocol 1; n = 37). The effects of bFGF or placebo (2.5 mug IV once a week) were also studied in animals fed a 0.2% cholesterol diet and sacrificed at 3 months (protocol 2; n = 18). Results were compared to those of rabbits fed with a normal chow (normal animals). Results: In protocol 1, bFGF administration for 5 weeks was associated with an improvement in endothelial function (p < 0.05), with a decrease in VCAM-1 expression (p = 0.03) and in the macrophage content of the plaque (p = 0.02). This preventive effect was lost at 10 weeks. In protocol 2, bFGF was associated with similar "beneficial" endpoints as observed at 5 weeks in protocol 1. Conclusions: Administration of bFGF is associated with important beneficial structural and functional effects in the early stage of experimental atherosclerosis. These results may help us to understand the role of growth factors in atherosclerosis and to anticipate their effects in human arteries.