Lawrence L. Rudel

Professor of Biochemistry and Comparative Medicine
B.S. Colorado State University, 1963
M.S., Ph.D. University of Arkansas Medical Center, 1965-1969 (Biochemistry)
Telphone: (336) 716-2821; E-mail: lrudel@wfubmc.edu

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.

Recent Publications:

Wallace JM, Schwarz M, Coward P, Houze J, Sawyer JK, Kelley KL, Chai A, Rudel LL. Effects of peroxisome proliferator-activated receptor alpha /delta agonists on HDL-cholesterol in vervet monkeys. J Lipid Res. 2005, In press.

Lada AT, Davis M, Kent C, Chapman J, Tomoda H, Omura S, Rudel LL. Identification of ACAT1- and ACAT2- specific inhibitors using a novel, cell-based fluorescent assay: evidence defining uniqueness for individual ACATs. J Lipid Res, 2004; 45:378-386.

Parini P, Davis M, Lada AT, Erickson SK, Wright TL, Gustafsson U, Sahlin S, Einarsson C, Eriksson M, Angelin B, Tomoda H, Omura S, Willingham MC, Rudel LL. ACAT2 is localized to hepatocytes and is the major cholesterol esterifying enzyme in human liver. Circ. 2004;110:2017-2023.

Lee RG, Kelley KK, Sawyer JK, Farese RV,Jr., Parks JS, and Rudel LL. Plasma cholesteryl esters provided by lecithin:cholesterol acyltransferase and acyl-Coenzyme A:cholesterol acyltransferase 2 have opposite atherogenic potential. Circ. Res. 2004;95:998-1004.

Willner, EL, Tow B, Buhman KK, Wilson M, Sanan D, Rudel LL, and Farese RV, Jr. Deficiency of acyl CoA:cholesterol acyltransferase 2 prevents atherosclerosis in apolipoprotein E-deficient mice. Proc Natl Acad Sci USA 2003; 100:1262-1267.

Temel RE, Gebre AK, Parks JS, Rudel LL. Compared to ACAT1 and LCAT, ACAT2 displays the greatest capacity to differentiate cholesterol from sitosterol. J Biol Chem, 2003;278:47594-47601.

Rudel LL, Davis M, Sawyer J, Shah R, Wallace J. Primates highly responsive to dietary cholesterol up-regulate hepatic ACAT2, and less responsive primates do not. J Biol Chem, 2002 277:31401-31406.