Connective tissue components play an important role in maintaining integrity of cardiovascular (C-V) structures in a variety of C-V diseases. This research concerns carbohydrate-protein macromolecules, proteoglycans and glycoprotens, found in the arterial wall and changes these complex carbohydrates undergo in atherosclerosis and diabetes mellitus. Investigations center on improving methods for characterization of aorta proteoglycans and gaining information on their biologic properties. A hybrid chondroitin sulfate=dermatan sulfate proteoglycan, partly characterized, is closely linked with collagen. The monomer, when intact, demonstrates anticoagulant activity, inhibition of platelet aggregation, lipoprotein lipase activation, and specific interaction with plasma apoB-containing lipoproteins. Any alteration o te proteoglycan macromolecule (protein core or glycosaminoglycan chains) critically reduces biologic properties. A heparan sulfate proteoglycan(s), which is more closely associated with aorta elastin, need investigation for similar biologic properties. Observations in vivo lipoprotein-proteoglycan complexes suggest an entrapment mechanism for lipid accumulation in pathogenesis of atherosclerosis. We plan to explore mechanisms of complexing in diet-induced atherosclerosis in experimental animal models undergoing induction and regression. Studies of biosynthesis of proteoglycans in organ culture are planned with factors that influence cellular activity. Initial observations show higher 35S uptake by dermatan sulfate chains, but a greater release rate of heparan sulfate proteoglycan(s). Corollary studies of aorta glycoproteins will be conducted to improve characterization of these complex carbohydrates. The potential role of nonenzymatic glycosylation within tissue, in he pathogenesis of vascular disease in diabetes, will be researched. Other studies concern mechanisms of antiatherogenicity of heparin and heparin-like compounds. The overall aim of this program is to evaluate the characteristics of C-V connective tissue carbohydrate macromolecules in an attempt to define more precisely the role these macromolecules play in C-V disease. Such information ultimately will improve approaches to treatment and prevention of heart disease.
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