Regulation of vascular smooth muscle cell growth by endothelial-synthesized extracellular matrices.
Previous work has demonstrated that aortic endothelial cells (EC) produce a heparin-like inhibitor of smooth muscle cell (SMC) growth when both cell types were cultured on plastic. We have now tested the influence of the extracellular matrix on this EC-SMC interaction. Specifically, we examined: 1) the role of different substrates (plastic, fibronectin, monomeric, and fibrillar collagens I and III, and EC-derived matrices) on the growth rate and population density of SMC; 2) the heparin-sensitivity of SMC on these diverse substrates; and 3) the effect of these same substrates on EC ability to secrete heparin-like and polypeptide inhibitors of SMC growth. SMC demonstrated a sixfold difference in sensitivity to heparin when grown on different substrates, with the following rank order: EGTA matrix greater than collagens = plastic = fibronectin greater than deoxycholic acid (DOC) matrix. Maximally, we found a 10-fold difference in the potency of the inhibitory activity secreted by EC grown on different substrates, with the following order: plastic = EGTA matrix greater than fibronectin greater than collagens = DOC matrix. Treatment of the conditioned mediums with heparinase and trypsin indicated that 58% to 76% of the inhibitory activity was due to heparin-like species, and 24% to 42% was due to protein(s). When EC cultured on EGTA matrix are compared to those pleated on DOC matrix, the potency of the heparin-like and peptide inhibitory activities increased 8- and 17-fold, respectively. Hypothetically, one would predict a 60-fold change in the potency of the antiproliferative effect if the contributions of substrate to EC production of inhibitors and SMC sensitivity were additive.(ABSTRACT TRUNCATED AT 250 WORDS)
Herman
I M
IM
Department of Anatomy and Cellular Biology, Tufts University School of Medicine, Boston, Massachusetts 02111.
Castellot
J J
JJ
D000818:Animals; D001011:Aorta / Q000166:cytology; D002417:Cattle; D002478:Cells, Cultured; D003470:Culture Media; D004730:Endothelium, Vascular / Q000378:metabolism*; D005109:Extracellular Matrix / Q000502:physiology*; D006493:Heparin / Q000494:pharmacology; D066298:In Vitro Techniques; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains
D003470:Culture Media; D006493:Heparin