ENDOTHELIAL CELL-CONDITIONED MEDIUM DOWN-REGULATES SMOOTH-MUSCLE CONTRACTILE PROTEIN EXPRESSION

Smooth muscle cells (SMC) within atherosclerotic lesions proliferate a nd exhibit phenotypic modulation, but the contribution of vascular end othelium to this process is poorly understood. Our aim was to examine the effects of endothelial cell-conditioned medium (ECCM) on vascular SMC growth and differentiation. Rat aortic ECCM stimulated a ninefold increase in [H-3]thymidine incorporation and downregulated smooth musc le-specific myosin heavy chain and cu-actin synthesis in rat aortic SM C. These effects were not inhibited by antibodies to platelet-derived growth factor (PDGF)-BB or PDGF-AB or with a PDGF beta-receptor subuni t. Treatment with PDGF-BB (at a concentration found in ECCM). PDGFAA, basic fibroblast growth factor, endothelin-1, or transforming growth f actor-beta did not reproduce these effects. The ECCM activities were s ensitive to heat and trypsinization, were >30 kDa in molecular mass, a nd bound weakly to heparin-Sepharose. Our data indicate that cultured endothelial cells produce a factor(s) that downregulates contractile p rotein expression in SMC, which may contribute to SMC dedifferentiatio n and proliferation.