Impact of MPO in Tobacco-related Cardiovascular Disease

Institution:	Sidney Kimmel Cancer Center
Investigator(s):	Wanda Reynolds, Ph.D.
Award Cycle:	2007 (Cycle 16)	Grant #: 16RT-0184	Award: $545,359
Subject Area:	Cardiovascular Disease
Award Type:	Research Project Awards

Abstracts

Initial Award Abstract

Exposure to tobacco smoke increases risk for cardiovascular disease, the leading cause of premature death in industrialized countries. While the mechanism is not well understood, an important component appears to be an increased production of oxidants. Myeloperoxidase (MPO) is an oxidant-generating enzyme also linked to increased risk of cardiovascular disease. This proposal investigates the links between MPO and tobacco-related cardiovascular disease and atherosclerosis, the accumulation of fat-filled macrophages (white blood cells) in the walls of blood vessels. MPO is expressed by white blood cells, and catalyzes a reaction between chloride and hydrogen peroxide, giving rise to hypochlorous acid (HOCl), the active component in bleach. HOCl is a toxic anti-microbial agent which plays an important role in innate immunity. However, the release of HOCl at inflammatory sites, such as atherosclerotic lesions in blood vessels, can lead to increased atherosclerosis. MPO-HOCl in lesions also kills the endothelial cells which cap the lesions, leading to rupture and heart attacks. Tobacco smoking increases the levels of MPO in blood serum. High serum MPO correlates with increased risk of cardiovascular disese and atherosclerosis. Here we propose to investigate the mechanism by which tobacco smoke increases MPO levels in blood serum, and the oxidative damage due to increased MPO production in smokers. We will also determine if tobacco smoke exposure leads to increased expression of the MPO gene, which could lead to novel therapeutics to reduce oxidative damage due to tobacco smoke, reducing risk of cardiovascular disease.

Publications

Toward targeted ¹³C Hyperpolarized MR Biosensors. Angewandte Chemie. Authors-Perman,W Tan, C Weitekamp, D Ross, B Bharracharya
Periodical: Angewandte Chemie (International Ed. in English)			Index Medicus:
Authors: Chekmenev, ET Reynolds, WF;Chow, SK Hovener, J; Northon, VA; Tran, T; Chan, HC; Wagner, S				ART
Yr: 2009	Vol:	Nbr:	Abs:	Pg: 10.1002/anie200

Toward targeted ¹³C Hyperpolarized MR Biosensors. Angewandte Chemie. Authors-Perman,W Tan, C Weitekamp, D Ross, B Bharracharya
Periodical: Angewandte Chemie (International Ed. in English)			Index Medicus:
Authors: Chekmenev, ET Reynolds, WF;Chow, SK Hovener, J; Northon, VA; Tran, T; Chan, HC; Wagner, S				ART
Yr: 2009	Vol:	Nbr:	Abs:	Pg: 10.1002/anie200