Principal Investigator: Sanjay Srivastava
Funding Mechanism: National Institutes of Health-TCORS Grant
ID number: 1P50HL120163-01
Award Date: 9/19/2013
Institution: University of Louisville
Tobacco use is associated with an increase in cardiovascular disease risk factors; however, tobacco constituents that mediate the cardiovascular toxicity of tobacco use remain largely unknown. Biomarkers of tobacco-induced cardiovascular injury associated with exposure to cigarette smoke, smokeless tobacco and their constituents may inform the FDAs regulation of tobacco products to protect public health. This project will identify biomarkers of tobacco product exposure and relate them to biomarkers of cardiovascular injury in a well-controlled animal model. To determine the relationship between these two sets of biomarkers, investigators will identify metabolites of tobacco constituents, establish their relationship with the extent and duration of exposure, and determine how they are related to the extent of cardiovascular injury. Specific aims are: (1) to examine tobacco-induced endothelial injury in adult mice exposed to varying intensities of tobacco smoke and smokeless tobacco; and (2) to delineate the contribution of harmful and potentially harmful (HPHC) constituents, such as aldehydes, to endothelial injury induced by tobacco exposure, by examining changes in endothelial injury biomarkers in mice exposed to individual constituents (i.e., nicotine, acrolein and crotonaldehyde). This project will provide information regarding how tobacco products could be evaluated for cardiovascular toxicity and how product constituents might be regulated to reduce the risk of cardiovascular injury.