Effect of Organophosphate Exposure on Cholesteryl Ester Hydrolase (sponsored by NIH)
Cardiovascular disease (CVD) in its various forms is the leading cause of death in the United States. Reverse cholesterol transport is a mechanism by which cholesterol present in atherosclerotic plaques within arterial walls is transported to the liver via high density lipoprotein particles for excretion in bile. Recent studies have suggested that human cholesteryl ester hydrolase (CEH), an enzyme that metabolizes cholesteryl esters, plays an important role in the regulation of reverse cholesterol transport. Our long term goal is to understand the role that environmental toxicants such as agricultural chemicals play in human disease. Three commonly used organophosphate (OP) insecticides will be used in this study. The goal of this project is to determine if exposure to OP insecticides will inhibit the CEH-catalyzed metabolism of cholesteryl esters, which could therefore increase the risk of developing atherosclerosis. The results from this study will provide preliminary insights into whether OP oxon metabolites can directly alter the structure-function of an enzyme involved in cholesterol metabolism, thus leading to an increased probability of a pathological outcome (i.e. atherosclerosis).