Atherosclerosis May Be Reduced by Inhibiting an Enzyme

A recent study has found that the enzyme acyl CoA:cholesterol acyltransferase 2 (ACAT2) is a major contributor to the formation of the cholesterol-rich plaques that accumulate in blood vessels and cause atherosclerosis. The study was published January 21, 2003, in the online edition of the Proceedings of the National Academy of Sciences.

Investigators from Wake Forest University Baptist Medical Center (Winston-Salem, NC, USA) and the University of California, San Francisco (USA) genetically engineered a line of mice without ACAT2, which catalyzes the formation of cholesterol esters in the liver and small intestines.

They found that total cholesterol levels were nearly two and a half times lower in the mice without ACAT2 than in the control mice, while the control mice had three and a half times more cholesterol esters in their blood. Mice without ACAT2 also absorbed less cholesterol from the intestines, and gallstone formation was limited. Circulating lipoproteins in these mice contained primarily triglycerides rather than cholesterol esters.

The results of this study reveal the crucial role of ACAT2-derived cholesterol esters in the development of atherosclerosis in mice and suggest that triglyceride-rich lipoproteins are not as atherogenic as those containing cholesterol esters.

"Our results support the rationale of pharmacologic inhibition of ACAT2 as a possible therapy for atherosclerosis,” said contributing author Dr. Lawrence L. Rudel, professor of comparative medicine and biochemistry at Wake Forest.





Related Links:
WakeForest U. Baptist Medical Center
Univ of California, San Francisco