Experiments of this proposal will test the hypothesis that 17 beta-estradiol preserves normal endothelial control of vascular tone in hypercholesterolemia by limiting modification of low-density lipoproteins and production of superoxide, thereby, preserving the actions of endothelium-derived relaxing factor. The investigation of the antioxidant effects of estrogen at physiological concentrations are proposed. The first specific aim is to characterize the effect of endogenous estrogens, estrogen replacement and estrogen withdrawal on the responses of the coronary arteries in animals fed a hypercholesterolemic diet using standard organ chamber techniques. The second specific aim will be to investigate how estrogens modify serum and membrane lipoproteins. The third specific aim will be to investigate the cellular mechanisms responsible for estrogen mediated modulation of coronary arterial responses including oxidation of low-density lipoprotein and production of superoxide.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL052936-03
Application #
2735248
Study Section
Experimental Cardiovascular Sciences Study Section (ECS)
Project Start
1996-07-01
Project End
2001-06-30
Budget Start
1998-07-01
Budget End
1999-06-30
Support Year
3
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Boston University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
604483045
City
Boston
State
MA
Country
United States
Zip Code
02118
Vita, Joseph A (2005) Polyphenols and cardiovascular disease: effects on endothelial and platelet function. Am J Clin Nutr 81:292S-297S
Widlansky, Michael E; Gokce, Noyan; Keaney Jr, John F et al. (2003) The clinical implications of endothelial dysfunction. J Am Coll Cardiol 42:1149-60
Vita, Joseph A; Gokce, Noyan; Duffy, Stephen J et al. (2003) Effect of atorvastatin on endothelium-dependent vasodilation in patients with coronary artery disease. Am J Cardiol 91:857-60
Duffy, Stephen J; Vita, Joseph A (2003) Effects of phenolics on vascular endothelial function. Curr Opin Lipidol 14:21-7
Eberhardt, Robert T; McMahon, Lillian; Duffy, Stephen J et al. (2003) Sickle cell anemia is associated with reduced nitric oxide bioactivity in peripheral conduit and resistance vessels. Am J Hematol 74:104-11
Kuvin, Jeffrey T; Gokce, Noyan; Holbrook, Monika et al. (2003) Effect of short-term antibiotic treatment on Chlamydia pneumoniae and peripheral endothelial function. Am J Cardiol 91:732-5
Gokce, Noyan; Keaney Jr, John F; Hunter, Liza M et al. (2003) Predictive value of noninvasively determined endothelial dysfunction for long-term cardiovascular events in patients with peripheral vascular disease. J Am Coll Cardiol 41:1769-75
Vita, Joseph A (2003) Tea consumption and cardiovascular disease: effects on endothelial function. J Nutr 133:3293S-3297S
Amar, Salomon; Gokce, Noyan; Morgan, Sonia et al. (2003) Periodontal disease is associated with brachial artery endothelial dysfunction and systemic inflammation. Arterioscler Thromb Vasc Biol 23:1245-9
Kahn, David F; Duffy, Stephen J; Tomasian, Douglas et al. (2002) Effects of black race on forearm resistance vessel function. Hypertension 40:195-201

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