Human acyl-CoA:cholesterol acyltransferase (ACAT) and its potential as a target for pharmaceutical intervention against atherosclerosis.
Acyl-CoA:cholesterol acyltransferase (ACAT) catalyzes the formation of cholesteryl esters from cholesterol and long-chain fatty-acyl-coenzyme A. At the single-cell level, ACAT serves as a regulator of intracellular cholesterol homeostasis. In addition, ACAT supplies cholesteryl esters for lipoprotein assembly in the liver and small intestine. Under pathological conditions, the accumulation of cholesteryl esters produced by ACAT in macrophages contributes to foam cell formation, a hallmark of the early stage of atherosclerosis. Several reviews addressing various aspects of ACAT and ACAT inhibitors are available. This review briefly outlines the current knowledge on the biochemical properties of human ACATs, and then focuses on discussing the merit of ACAT as a drug target for pharmaceutical interventions against atherosclerosis.
Chang
Catherine
C
Department of Biochemistry, Dartmouth Medical School, Hanover, New Hampshire 03755, USA. Catherine.Chang@dartmouth.edu
Dong
Ruhong
R
Miyazaki
Akira
A
Sakashita
Naomi
N
Zhang
Yi
Y
Liu
Jay
J
Guo
Michael
M
Li
Bo-Liang
BL
Chang
Ta-Yuan
TY
D000214:Acyl Coenzyme A / Q000378:metabolism*; D050197:Atherosclerosis / Q000188:drug therapy / Q000201:enzymology / Q000517:prevention & control; D001692:Biological Transport; D002462:Cell Membrane / Q000378:metabolism; D002788:Cholesterol Esters / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D006706:Homeostasis; D006801:Humans; D000960:Hypolipidemic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D007150:Immunohistochemistry; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D002785:Sterol O-Acyltransferase / Q000037:antagonists & inhibitors* / Q000378:metabolism
D000214:Acyl Coenzyme A; D002788:Cholesterol Esters; D004791:Enzyme Inhibitors; D000960:Hypolipidemic Agents; D002785:Sterol O-Acyltransferase