Endothelial cell cytotoxicity in inflammatory vascular diseases--the possible role of oxidised lipoproteins.
One of the proposed mechanisms of vascular damage in connective tissue disease is the direct action of a cytotoxic serum factor inducing endothelial cell damage. The nature of this serum factor is unclear, but has been suggested to be a lipoprotein. Sera from patients with (1) systemic necrotising arteritis (polyarteritis nodosa, Wegener's granulomatosis, and necrotising arteritis associated with rheumatoid synovitis), (2) systemic or joint restricted rheumatoid disease, and (3) large vessel/giant cell arteritis have been examined for cytotoxicity to human cultured endothelial cells and azide-resistant ferroxidase-like activity (indicative of the oxidised lipoprotein content). Stored sera from patients with necrotising arteritis showed a significantly enhanced tendency to develop oxidised lipoprotein, which correlated closely with human endothelial cell cytotoxicity. Fresh sera also contained this factor, but to a lesser extent. It is argued that the cytotoxic factor detected in previous clinical studies is in part an in-vitro artefact, although its accelerated development in certain patient groups might suggest an excess of pro-oxidants that have developed in vivo.
D001167:Arteritis / Q000097:blood / Q000276:immunology*; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000276:immunology; D001386:Azides / Q000494:pharmacology; D002470:Cell Survival; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D004727:Endothelium / Q000166:cytology / Q000276:immunology*; D006801:Humans; D008074:Lipoproteins / Q000097:blood / Q000276:immunology*; D010084:Oxidation-Reduction
D001386:Azides; D008074:Lipoproteins