P-108 Regulation of proteoglycan synthesis by basic fibroblast growth factor in cultured vascular smooth muscle cells

Proteoglycan synthesis by vascular smooth muscle cells is regulated by growth factors/cytokines such as platelet-derived growth factor and transforming growth factor-β, and the regulation has been implicated in progression of atherosclerosis. To address the question of whether or not basic fibroblast growth factor (FGF-2) regulates the proteoglycan synthesis, dense and sparse cultures of bovine aortic smooth muscle cells was treated with recombinant human FGF-2 in the presence of [35S]sulfate or 35S-labeled amino acids, and labeled proteoglycans were characterized by DEAE-Sephacel ion exchange chromatography and Sepharose CL-2B molecular sieve chromatography. The glycosaminoglycan Mr and composition were analyzed by Sepharose CL-6B chromatography and fluorophore-assisted carbohydrate electrophoresis. Core proteins and their mRNA levels were determined by SDS-polyacrylamide gel electrophoresis/Western blot analysis and quantitative RT-PCR, respectively. These experiments indicate that FGF-2 induces the synthesis of biglycan and decorin, small leucine-rich dermatan sulfate proteoglycans, particularly when the cell density is high. Furthermore, length of the dermatan sulfate chains from biglycan and decorin is unaffected by FGF-2 but biglycan has less iduronic acid after exposure to FGF-2. Since biglycan and decorin excessively accumulate in atherosclerotic plaques and biglycan from the plaques contains reduced amount of iduronic acid, FGF-2 may contribute to such changes in the lesion.