968-27 Basic Fibroblast Growth Factor has Potent Selective Effects on Collagen Gene Expression by Human Vascular Smooth Muscle Cells

Basic fibroblast growth factor (bFGF) is a smooth muscle cell (SMC) mitogen known to playa role in the early response of the vessel wall to balloon injury. During this initial stage, remodeling of the extracellular matrix (ECM), including collagen, is necessary for cell proliferation, migration and lesion expansion. We therefore determined the effect of bFGF on fibrillar collagen gene expression by human vascular SMCs.SMCs, cultivated from internal mammary artery, were serum-deprived and incubated with bFGF (50ng/ml) or vehicle. Collagen synthesis rate was determined by labeling cultures with [3H]proline, separating proteins byelectrophoresis, and visualizing and quantifying bands by fluorography and laser densitometry, respectively. This revealed a significant, net decrease in collagen synthesis induced by bFGF. To determine the mechanism of this response, the effect of bFGF on collagen mRNA was determined by Northern blot analysis using probes specific for α-chains of collagen types I, III, and V, accounting for the major and minor fibrillar collagens found in human atherosclerotic plaque. Cell proliferation was assessed by probing for histone 3.2. Despite a consistent increase in SMC proliferation, bFGF reduced expression of α1 (I) collagen mRNA by upto 90%. In contrast, bFGF increased expression of α1(III) and α2(V) collagen mRNA by approximately 20%. Because type III and V collagen fibers are finer than type I, the divergent results may reflect a shift to a less mature collagen lattice induced by bFGF.ConclusionTotal fibrillar collagen synthesis by human SMCs is reduced by bFGF, due to a potent selective inhibition of type I collagen expression. This effect of bFGF on the ECM may be a prerequisite for SMC accumulation and lesion formation following balloon angioplasty