Heparin and related glycosaminoglycans modulate the secretory phenotype of vascular smooth muscle cells

Abstract

Previous studies have established a role for heparin-like molecules in the regulation of vascular smooth muscle cell growth and migration in vitro. We present data indicating that the secretory phenotype of cultured rat aortic smooth muscle cells can be modulated by exogenous soluble heparin, heparan sulfate, and dermatan sulfate glycosaminoglycans. In the presence of these molecules, smooth muscle cells secrete increased amounts of two noncollagenous proteins (Mr 37,000 and 39,000). This effect can be mimicked by iota carrageenan and dextran sulfate but not by hyaluronic acid, chondroitin-4-sulfate, or chondroitin-6-sulfate. The inductive effect of heparin was dose-dependent and occurred rapidly (within 1 h) with maximal induction (three- to fivefold over controls) occurring after 10-12 h of treatment. The effect was rapidly reversible (within 1 h) and was not altered in the presence of actinomycin D, suggesting regulation at a posttranscriptional level. These data indicate that the biosynthetic expression of specific smooth muscle cell proteins may be determined, at least in part, by components of the smooth muscle cell extracellular matrix.