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There is a strong positive correlation between chronic exposure to tobacco smoke and an increased incidence of atherosclerosis and its clinical sequelae: coronary artery disease, peripheral vascular disease, and stroke. In fact, atherosclerosis is one of the primary causes of death amongst tobacco smokers. Conversely, high density lipoprotein (HDL), otherwise known as the "good cholesterol" is correlated with a reduced risk for atherosclerosis. This is due in large part to HDL's ability to remove cholesterol from atherosclerotic plaques and deliver it to the liver for excretion through the bile. The ability of HDL to perform this function is the best known correlate with a reduced risk for atherosclerosis. As a result, an assay that could measure this parameter of a patient's HDL function, namely its capacity remove cholesterol from atherosclerotic plaques, would be a strong predictor of risk for atherosclerosis.
In this proposal we will employ our newly developed assay that measures the effectiveness of HDL to examine the effect of tobacco smoke exposure and its inflammatory by products on HDL's ability to mobilize cholesterol. The assay employed is a new, rapid (10 minutes), convenient (requires only a drop of blood), and cost effective means of determining the effectiveness of a person's HDL at preventing atherosclerosis.
Results from this work will establish a method for the early detection of the onset of atherosclerosis, particularly due to the loss of HDL function as a result of tobacco smoke exposure. Furthermore, such an assay could provide a significant deterrent as smokers can directly and immediately observe the negative effects of smoking on processes that contribute to cardiovascular health. More importantly, by monitoring recovery of HDL function after cessation of smoking, our assay could provide considerable positive reinforcement.
Furthermore, our method of evaluating HDL function has significant applications for both basic and clinical research; identifying atherosclerosis-relevant HDL modifying processes in the areas of pharmacology (identification of HDL-directed therapeutics), diagnosis (predicting risk for atherosclerosis in patients), nutrition (identifying healthy diets), and public policy; all of which are highly relevant to current and former smokers. |
