LIPOPROTEIN-PROTEOGLYCAN INTERACTIONS IN DIABETES

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This project proposes to investigate the potential role of diabetes on the interaction between lipoproteins and extracellular proteoglycans of the artery wall, alterations of which might account for the increased atherosclerosis risk typical of diabetes. Studies will be undertaken to determine whether alterations in either lipoproteins or proteoglycans that might occur in diabetes will modify their interaction in such a manner that would result in the increased retention of lipoproteins in the artery wall. Features common to IDDM and NIDDM such as lipoprotein oxidation, non- enzymatic glycation of proteins, altered matrix gene expression, and development of renal complications are hypothesized to alter lipoprotein- proteoglycan interaction. These interactions may also be affected by the presence and nature of intermediary molecules such as apo E and lipoprotein lipase (LPL). Lipoprotein-proteoglycan interactions will be evaluated by in vitro experiments, by studying lipoproteins from subjects with diabetes and renal complications, and proteoglycan from subjects and renal complications, and proteoglycans from arteries of subjects with diabetes. Project 2 is part of an integrated program aimed at providing further understanding of the mechanisms of accelerated macrovascular disease in diabetes. As such, it interacts with each of the four other projects in this Program Project.