Metabolic consequences of tobacco toxicants

Smoking is strongly associated with a marked increase in cardiovascular disease, yet the mechanisms by which tobacco use results in cardiovascular disease remain unknown. Prior work from our laboratory has suggested that tobacco use results in dysregulation of metabolism, with profound changes in circulating metabolites in the blood. We postulate that these metabolic changes contribute to the accelerated cardiovascular disease observed in smokers. In this Tobacco-Related Disease Research Program grant, we propose to use cutting-edge mass spectrometry to comprehensively measure the hundreds to thousands of blood metabolites that are changed in humans with smoking. Secondly, we will determine which of these tobacco-related metabolite changes are associated with the development of cardiovascular disease in large human clinical cohorts. This work will provide unprecedented insights into the metabolic consequences of smoking, the role of metabolic dysregulation in human cardiovascular disease, and the potential of metabolites to serve as early markers for identifying smokers at greatest risk for developing cardiovascular disease.