SERUM STIMULATION, CELL-CELL INTERACTIONS, AND EXTRACELLULAR-MATRIX INDEPENDENTLY INFLUENCE SMOOTH-MUSCLE CELL PHENOTYPE IN-VITRO

Vascular injury profoundly alters the vessel wall microenvironment, an d smooth muscle cells respond with cell cycle re-entry, loss of contra ctile elements, extracellular matrix remodeling, and altered signaling by endogenous growth factors and their receptors. Environmental cues include stimulation by exogenous mitogens and both cell-cell and cell- matrix interactions. Modeling this process in smooth muscle cells ia v itro, these environmental determinants were varied independently and t he phenotypic consequences assessed. Mitogenic stimulation with serum promoted the synthesis of collagen and fibronectin and the expression of fibroblast growth factor receptor-1 and suppressed the content of s mooth muscle alpha-actin, myosin heavy chain, and basic fibroblast gro wth factor. Low cell density (reduced cell-cell contact) was also asso ciated with enhanced extracellular matrix protein production, increase d fibroblast growth factor receptor-1 expression, and reduced contract ile protein and basic fibroblast growth factor content. The influence of serum stimulation and reduced cell-cell contact were independent an d additive. Provision of a type I collagen matrix blunted the influenc e of serum and cell-cell contact on collagen synthesis but had minor e ffects on other measures of phenotype. Environmental factors thus inde pendently influence smooth muscle cell phenotype, including endogenous growth factor expression and responsiveness, which can in turn influe nce the microenvironment of the vessel wan after injury.