Modulation of extracellular matrix gene expression by heparin and endothelial cell growth factor in human smooth...

We have previously shown that human vascular smooth muscle cells grown for several passages in the presence of heparin and endothelial cell growth factor (ECGF) exhibit profound alterations in the synthesis of extracellular matrix proteins. In the present study, we demonstrate that the mRNA steady-state levels for various matrix macromolecules were altered in the presence of heparin and ECGF, but not ECGF alone. Specifically, the expression of types I and IV collagens, fibronectin, and decorin proteoglycan genes were markedly inhibited, whereas that of versican proteoglycan and beta-actin genes were unaffected. The effects were fully reversible. The suppression of the collagen gene expression was related to decreased collagen production by cells incubated with heparin and ECGF. Thus, heparin and ECGF synergistically elicit a coordinate and selective inhibition of matrix gene expression in human smooth muscle cells.