Lawrence L. Rudel
Research into the causes of premature coronary heart disease has been the focus of the work in the Rudel laboratory for over 30 years. Nonhuman primate models of diet-induced atherosclerosis have been studied, and nutritional components of the diet including cholesterol and individual types of fatty acids have been evaluated. Both cholesterol and saturated fatty acids have been found to be proatherogenic while polyunsaturated fatty acids have been found to be antiatherogenic. Interestingly, monounsaturated fatty acids were also found to be proathergenic, and diets rich in monounsaturated fatty acids resulted in as much atherosclerosis as diets with saturated fatty acids. The work in monkeys suggested that cholesterol esterification in the liver is strongly associated with atherosclerosis progression, and the enzyme ACAT2 (acylCoA:cholesterol acyltransferase 2) was identified to be the enzyme in hepatocytes that catalyzes cholesterol esterification. Monounsaturated fatty acids appear to cause more ACAT2-mediated esterification of cholesterol. Work in mice made deficient in ACAT2 has shown that, in its absence, atherosclerosis development is greatly decreased. These data have suggested the hypothesis that by limiting available ACAT2 activity, prevention of premature coronary heart disease would be promoted, and additional work to develop this CHD prevention strategy is continuing.
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