The overall goal of this application is to provide support and training for the applicant towards becoming an independent, patient-oriented clinical investigator in the field of vascular biology. The proposed application builds on the applicant's previous research experience, provides new training, and examines a highly relevant clinical question conducted in a mentor-based environment ideally suited for the completion of this project. The overall objective of the proposed plan is to investigate the importance of examining endothelial function as a predictor of cardiovascular events in patients with atherosclerotic vascular disease. The vascular endothelium regulates vasomotor tone, platelet activity, and inflammation through the synthesis and elaboration of a number of factors including endothelium-derived nitric oxide (EDNO). Endothelium-dependent vasodilation and platelet inhibition are impaired in atherosclerosis and associated conditions, possibly due to increased vascular oxidative stress and reduced NO bioactivity. Loss of normal vascular endothelial function favors a local vasospastic, prothrombotic, and proinflammatory milieu, and is linked to the pathophysiology of cardiovascular events including myocardial infarction, stroke, and unstable angina. However, no study to date has demonstrated that impaired endothelial function is predictive of cardiovascular risk. Patients with peripheral arteriosclerotic disease undergoing vascular surgery have multiple risk factors for endothelial dysfunction, and are at high-risk for perioperative cardiovascular events. Using non- invasive, high-resolution vascular ultrasound analysis of brachial arterial vasomotor function, this project proposes in specific aim 1: to determine whether patients with impaired preoperative vascular endothelial function have increased cardiovascular events at the time of vascular surgery compared to patients with normal endothelial function, and in specific aim 2: to determine whether pretreatment of subjects with impaired endothelial function using the antioxidant ascorbic acid (Vitamin C) reduces perioperative cardiovascular events during vascular surgery. Identifying high-risk subjects with impaired vascular function may lead to potential improvement in management of these patients.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23HL004425-05
Application #
6782702
Study Section
Special Emphasis Panel (ZHL1-CSR-F (M1))
Program Officer
Schucker, Beth
Project Start
2000-09-01
Project End
2006-07-31
Budget Start
2004-08-01
Budget End
2006-07-31
Support Year
5
Fiscal Year
2004
Total Cost
$124,767
Indirect Cost
Name
Boston Medical Center
Department
Type
DUNS #
005492160
City
Boston
State
MA
Country
United States
Zip Code
02118
Widlansky, Michael E; Duffy, Stephen J; Hamburg, Naomi M et al. (2005) Effects of black tea consumption on plasma catechins and markers of oxidative stress and inflammation in patients with coronary artery disease. Free Radic Biol Med 38:499-506
Gokce, Noyan (2004) L-arginine and hypertension. J Nutr 134:2807S-2811S; discussion 2818S-2
Vita, Joseph A; Brennan, Marie-Luise; Gokce, Noyan et al. (2004) Serum myeloperoxidase levels independently predict endothelial dysfunction in humans. Circulation 110:1134-9
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
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
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
Widlansky, Michael E; Price, Daniel T; Gokce, Noyan et al. (2003) Short- and long-term COX-2 inhibition reverses endothelial dysfunction in patients with hypertension. Hypertension 42:310-5
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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