STIMULATION OF GROWTH AND MIGRATION OF VASCULAR ENDOTHELIAL-CELLS BY VASCULAR ENDOTHELIAL GROWTH-FACTOR TRANSDUCED SMOOTH-MUSCLE CELLS IN COCULTURE

Vascular endothelial growth factor (VEGF) is a secreted mitogen with h igh specificity toward endothelial cells. Expression of VEGF by smooth muscle cells in vivo may be an important stimulus for the regrowth of the endothelium after damage caused by interventions such as angiopla sty. The levels of VEGF secreted by cultured smooth muscle cells minim ally stimulated growth of endothelial cells in co-culture. Full length cDNA for the 165 amino acid residue, bovine VEGF (VFGF(165)), was iso lated from calf liver total RNA by reverse transcriptase polymerase ch ain reaction (RT-PCR) techniques, and used to generate plasmid constru cts for transfection. Bovine aortic smooth muscle cells (BSMC), stably transfected with VFGF(165) plasmid DNA, secreted mitogen into conditi oned culture medium at levels that are physiologically relevant (2-4 n g/ml). Transformed BSMC stimulated growth of bovine aortic endothelial cells (BAEC) in co-culture, to a significantly greater extent than mo ck transfected BSMC, Migration of BAEC was also enhanced by the presen ce of VEGF transduced BSMC. These data suggest that smooth muscle cell s, genetically engineered to produce VEGF, may provide biologic lining s in cardiovascular prostheses that could promote the growth of endoge nous endothelial cells.