Growth Factor Effects on Cells of the Vascular Wall: A Survey

Abstract

Acidic and basic fibroblast growth factors (aFGF, bFGF), platelet-derived growth factor (PDGF), epidermal growth factor (EGF), and transforming growth factor type beta (TGF-beta) are well-characterized growth regulators. Though there are reports of the effects of some of these factors on vascular cells, variability in the purity of growth factor preparations and differing cell culture conditions make comparison among the results difficult. Thus, a study employing homogeneous preparations of recombinant growth factors on well-characterized cell populations was conducted. Each of the factors was tested for its effect on the proliferation of cells derived from large and small blood vessels: aortic and capillary endothelial cells (EC), smooth muscle cells (SMC) and pericytes. Of the five growth factors only bFGF stimulated the proliferation of both large vessel and microvessel EC; aFGF was mitogenic for microvessel but not large vessel EC. Neither PDGF (AA, BB or AB) nor EGF had any effect on EC growth. TGF-beta was a potent inhibitor of both aortic and capillary EC proliferation with half maximal inhibition at concentrations as low as 0.05 and 0.25 ng/ml for microvessel and aortic EC, respectively. The FGFs were potent mitogens for the mural cells, SMC and pericytes. Likewise, PDGF was stimulatory for SMC and pericytes. The BB homodimer yielded the greatest degree of growth stimulation for both pericytes and SMC. In the case of SMC the AA homodimer stimulated small but significant growth and the effect of AB was intermediate to that of the homodimeric forms. On the other hand, neither the AA homodimer nor the heterodimer stimulated any significant increase in pericyte number. EGF was moderately mitogenic for both types of mural cells, reaching maximum stimulation at 100 pg/ml of EGF. TGF-beta was inhibitory for SMC but not for pericyte proliferation. These data indicate both quantitative and qualitative differences between the responses of large and small vessel EC to the various growth factors and distinct differences in the responsiveness of SMC and pericytes to PDGF and TGF-beta.