INCREASED LIPID-PEROXIDATION IN CYCLOSPORINE-TREATED HEART-TRANSPLANT RECIPIENTS

Accelerated coronary artery disease has emerged as the major limiting factor for long-term success of heart transplantation, and traditional risk factors have not been etiologically important.1 Lipid peroxides have been implicated in the initiation of atherogenesis.2 Although the sequence of molecular and cellular changes in this process has not been elucidated, it has been proposed that chemically reactive lipids released during lipid peroxidation modify: (1) membrane constituents inducing potentially thrombotic platelet disorders3; and (2) circulating lipoprotein, thus altering clearance and intraarterial deposition of lipoprotein-derived cholesterol.4 Malondialdehyde (MDA) is one product of lipid peroxidation. Reaction of MDA with a critical number of lysine residues results in formation of 1-amino-3-iminopropene bridges, and protein breakdown. The portion of the proteins that are shed into the plasma are called Schiff bases and can be quantitated by fluorescence measurements.5 Studies in vitro or in animal model of atherosclerosis have implicated MDA modification of lipoproteins as potential mechanisms of atherogenesis.4 Whether modification of protein by MDA or other lipid peroxides occurs in vivo in humans has yet to be demonstrated. One approach to resolve this issue is through identification of plasma antibody directed against modified proteins. Recent studies have shown that normal human serum contains immunoglobulins with antibodylike specificity for MDA-modified proteins.6,7 This was the direct evidence of an in vivo protein modification resulting from lipid peroxidation. Thus, an ELISA technique able to quantitate these immunoglobulins was developed.8 In the present study, we have examined indicators of in vivo lipid peroxidation to assess the possibility of it increasing in accelerated coronary atherosclerosis occurring in patients after transplantation compared with patients with coronary artery disease without transplantation. © 1991.