Serum deprivation of vascular smooth muscle cells enhances collagen gene expression

Vascular smooth muscle cells produce the bulk of connective tissue protein in major arteries. Previously, we demonstrated that collagen synthesis by cultured bovine aortic smooth muscle cells in exponential growth is low and increases as cells approach confluence and growth slows. To evaluate more directly the effects of the proliferative state, subconfluent cultures of smooth muscle cells were incubated in medium supplemented with 0.5% fetal calf serum; under these conditions of growth factor deprivation, cells become quiescent within 72 h. The mRNA levels for type I and III collagens increased markedly within 12 h; at 48 h, they were between 2- and 15-fold higher than in cells growing exponentially. Upon addition of serum to quiescent cultures, cells re-entered the cycle, and collagen mRNA levels decreased. Expression of alpha 1(I), alpha 2(I), and alpha 1(III) mRNAs differed significantly, indicating differential gene regulation. In nuclear run-off assays, changes detected in collagen transcription were insufficient to account for changes in mRNA levels, suggesting additional post-transcriptional sites of control. The inverse response of collagen expression to the proliferative state suggests that exposure of smooth muscle cells in vivo to factors which influence their growth state could have profound effects on the structure of the arterial wall.