Inhibition of endothelial cell adhesion and proliferation by extracellularmatrix from vascular smooth muscle cells: role of type V collagen

Endothelial cells recovering from damage due to disease or surgical procedu res come into close contact with extracellular matrix (ECM) secreted by int imal vascular smooth muscle cells (VSMCs). We have investigated these relat ionships using human umbilical artery endothelial cells (HUAECs) and human mammary artery VSMC in vitro. HUAEC adhesion and proliferation were signifi cantly lower on ECM secreted by VSMC compared with HUAEC ECM or surface-coa ted fibronectin. Characterisation of the ECM of both cell types with monocl onal antibodies showed that the ECM secreted by VSMC contained significantl y more elastin, chondroitin sulphate and collagen types I, III and V than t hat from HUAECs. HUAECs adhered poorly to collagen type V coated on plastic and not at all to elastin. When these proteins were co-coated with fibrone ctin, elastin did not inhibit migration or proliferation compared to the re sponse on fibronectin but collagen type V significantly inhibited both. Tre atment of VSMC ECM with enzymes which selectively depleted the matrix of co llagen types I, III and IV, or chondroitin sulphate, had no effect on HUAEC responses to the ECM, suggesting that these molecules did not contribute t o the inhibition of HUAECs. Treatment of VSMC ECM with a mixture of collage nases, selectively depleted the matrix of collagen type V, as well as types I, III and IV. Such depleted ECMs supported increased proliferation of HUA ECs compared to buffer controls. Overall these results suggest that collage n V secreted into the ECM of VSMC may inhibit the recovery of adjacent endo thelium. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.