Inhibition of endothelial cell adhesion and proliferation by extracellular matrix from vascular smooth muscle cells: role of type V collagen.
Endothelial cells recovering from damage due to disease or surgical procedures come into close contact with extracellular matrix (ECM) secreted by intimal vascular smooth muscle cells (VSMCs). We have investigated these relationships using human umbilical artery endothelial cells (HUAECs) and human mammary artery VSMC in vitro. HUAEC adhesion and proliferation were significantly lower on ECM secreted by VSMC compared with HUAEC ECM or surface-coated fibronectin. Characterisation of the ECM of both cell types with monoclonal antibodies showed that the ECM secreted by VSMC contained significantly more elastin, chondroitin sulphate and collagen types I, III and V than that 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 fibronectin, elastin did not inhibit migration or proliferation compared to the response on fibronectin but collagen type V significantly inhibited both. Treatment of VSMC ECM with enzymes which selectively depleted the matrix of collagen types I, III and IV, or chondroitin sulphate, had no effect on HUAEC responses to the ECM, suggesting that these molecules did not contribute to the inhibition of HUAECs. Treatment of VSMC ECM with a mixture of collagenases, selectively depleted the matrix of collagen type V, as well as types I, III and IV. Such depleted ECMs supported increased proliferation of HUAECs compared to buffer controls. Overall these results suggest that collagen V secreted into the ECM of VSMC may inhibit the recovery of adjacent endothelium.
Underwood
P A
PA
CSIRO Division of Molecular Science, Sydney Laboratory and Co-operative Research Centre for Cardiac Technology, North Ryde, NSW, Australia. anne.underwood@molsci.csiro.au
Bean
P A
PA
Whitelock
J M
JM
D002448:Cell Adhesion / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D002478:Cells, Cultured; D002810:Chondroitinases and Chondroitin Lyases / Q000494:pharmacology; D003094:Collagen / Q000032:analysis / Q000502:physiology*; D017364:Collagenases / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology*; D005109:Extracellular Matrix / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D010196:Pancreatic Elastase / Q000494:pharmacology; D014469:Umbilical Arteries
D003094:Collagen; D010196:Pancreatic Elastase; D017364:Collagenases; D002810:Chondroitinases and Chondroitin Lyases