Smooth muscle cells produce an inhibitor of endothelial cell growth

A potent inhibitor of endothelial cell growth and neovascularization has previously been isolated from both bovine and human aorta. In an attempt to determine if the major cellular component of that tissue, smooth muscle cells, synthesized molecules with this activity, we studied the effects of serum-free conditioned medium from bovine aortic smooth muscle on the growth of cultured endothelial cells from bovine aorta. The smooth muscle conditioned medium was found to contain both growth inhibitory and stimulating activities that could be distinguished by their heat stability. The inhibitor is precipitable by ammonium sulfate, heat stable (80 degrees C), and inactivated by dithiothreitol, trypsin, and 2-mercaptoethanol. It has an estimated molecular weight of approximately 35,000 to 40,000 daltons (by column chromatography). It therefore appears that smooth muscle cells produce an inhibitor of endothelial cell growth that belongs to a class of natural endothelial cell growth inhibitors derived from avascular tissues we tentatively term "avasculins." Proof of its identity with the inhibitor isolated from intact aorta (or other tissues) must await purification.