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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL002942-29
Application #
3334155
Study Section
Pathobiochemistry Study Section (PBC)
Project Start
1977-04-01
Project End
1987-03-31
Budget Start
1985-04-01
Budget End
1986-03-31
Support Year
29
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Louisiana State University Hsc New Orleans
Department
Type
Schools of Medicine
DUNS #
782627814
City
New Orleans
State
LA
Country
United States
Zip Code
70112
Harville, Emily W; Jacobs, Marni; Shu, Tian et al. (2018) Feasibility of Linking Long-Term Cardiovascular Cohort Data to Offspring Birth Records: The Bogalusa Heart Study. Matern Child Health J 22:858-865
Harville, E W; Chen, W; Bazzano, L et al. (2017) Indicators of fetal growth and adult liver enzymes: the Bogalusa Heart Study and the Cardiovascular Risk in Young Finns Study. J Dev Orig Health Dis 8:226-235
Harville, Emily W; Jacobs, Marni B; Qi, Lu et al. (2017) Multigenerational Cardiometabolic Risk as a Predictor of Birth Outcomes: The Bogalusa Heart Study. J Pediatr 181:154-162.e1
Jacobs, M B; Harville, E W; Kelly, T N et al. (2016) Maternal apolipoprotein E genotype as a potential risk factor for poor birth outcomes: The Bogalusa Heart Study. J Perinatol 36:432-8