Human Acyl-CoA:Cholesterol acyltransferase (ACAT) and its potential as a target for pharmaceutical intervention against atherosclerosis

被引：46

作者：

Chang, C ^{[1
]}

Dong, RH

Miyazaki, A

Sadashita, N

Zhang, Y

Liu, J

Guo, M

Li, BL

Chang, TY

机构：

[1] Dartmouth Med Sch, Dept Biochem, Hanover, NH 03755 USA

[2] Showa Univ, Sch Med, Dept Biochem, Tokyo 142, Japan

[3] Kumamoto Univ, Sch Med, Dept Pathol, Kumamoto 860, Japan

[4] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, State Key Lab Mol Biol, Shanghai 200031, Peoples R China

来源：

ACTA BIOCHIMICA ET BIOPHYSICA SINICA | 2006年 / 38卷 / 03期

关键词：

acyl-CoA; cholesterol acyltransferase; cholesterol; cholesteryl ester; atherosclerosis;

D O I：

10.1111/j.1745-7270.2006.00154.x

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 [1-8]. 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.

引用

页码：151 / 156

页数：6

共 45 条

[1] Massive xanthomatosis and altered composition of atherosclerotic lesions in hyperlipidemic mice lacking acyl CoA:cholesterol acyltransferase 1 [J].

Accad, M ;

Smith, SJ ;

Newland, DL ;

Sanan, DA ;

King, LE ;

Linton, MF ;

Fazio, S ;

Farese, RV .

JOURNAL OF CLINICAL INVESTIGATION, 2000, 105 (06) :711-719

[2] Acyl coenzyme A:Cholesterol acyltransferase inhibitors as hypolipidemic and antiatherosclerotic drugs [J].

Alegret, M ;

Llaverias, G ;

Silvestre, JS .

METHODS AND FINDINGS IN EXPERIMENTAL AND CLINICAL PHARMACOLOGY, 2004, 26 (07) :563-586

[3] Identification of a form of acyl-CoA:cholesterol acyltransferase specific to liver and intestine in nonhuman primates [J].

Anderson, RA ;

Joyce, C ;

Davis, M ;

Reagan, JW ;

Clark, M ;

Shelness, GS ;

Rudel, LL .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (41) :26747-26754

[4] INFLUENCE OF HIGH-DENSITY LIPOPROTEIN ON ESTERIFIED CHOLESTEROL STORES IN MACROPHAGES AND HEPATOMA-CELLS [J].

BERNARD, DW ;

RODRIGUEZ, A ;

ROTHBLAT, GH ;

GLICK, JM .

ARTERIOSCLEROSIS, 1990, 10 (01) :135-144

[5] COMPARISON OF CI-976, AN ACAT INHIBITOR, AND SELECTED LIPID-LOWERING AGENTS FOR ANTIATHEROSCLEROTIC ACTIVITY IN ILIAC FEMORAL AND THORACIC AORTIC LESIONS - A BIOCHEMICAL, MORPHOLOGICAL, AND MORPHOMETRIC EVALUATION [J].

BOCAN, TMA ;

MUELLER, SB ;

UHLENDORF, PD ;

NEWTON, RS ;

KRAUSE, BR .

ARTERIOSCLEROSIS AND THROMBOSIS, 1991, 11 (06) :1830-1843

[6] Mammalian acyl-CoA: cholesterol acyltransferases [J].

Buhman, KF ;

Accad, M ;

Farese, RV .

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS, 2000, 1529 (1-3) :142-154

[7]

CADIGAN KM, 1988, J BIOL CHEM, V263, P274

[8] ACAT-2, a second mammalian acyl-CoA:cholesterol acyltransferase -: Its cloning, expression, and characterization [J].

Cases, S ;

Novak, S ;

Zheng, YW ;

Myers, HM ;

Lear, SR ;

Sande, E ;

Welch', CB ;

Lusis, AJ ;

Spencer, TA ;

Krause, BR ;

Erickson, SK ;

Farese, RV .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (41) :26755-26764

[9]

Chang CCY, 2000, J BIOL CHEM, V275, P28083

[10]

CHANG CCY, 1995, J BIOL CHEM, V270, P29532

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