Post-translational regulation of type I collagen synthesis by heparin in vascular smooth muscle cells

Heparin is a potent inhibitor of smooth muscle cell proliferation. It reduced the level of type I collagen by one-half in culture medium of smooth muscle cells, whereas it increased the type I collagen expression 4-fold in the cell layer compartment under the conditions where it inhibited cell proliferation. No significant change in the level of prolyl hydroxylation in the newly synthesized type I procollagen or steady-state levels of pro α₁ (I) and pro α₂(I) collagen mRNAs was detected after heparin treatment. Short-pulse and pulse-chase experiments revealed that heparin inhibited the secretion of type I procollagen and stimulated the accumulation of type I collagen in the extracellular space. These results suggest that heparin could modulate type I collagen expression at a posttranslational level. The modulation appeared to be closely related with its inhibitory effect on cell proliferation via two different mechanisms: the inhibition of the secretion of type I procollagen and stabilization of type I collagen in the cell layer. Heparin thus appears to be a multifunc tional modulator for cell proliferation and the expression of type I collagen in vascular smooth muscle cells.