期刊论文详细信息
Metabolites
Acyl-Coenzyme A: Cholesterol Acyltransferase (ACAT) in Cholesterol Metabolism: From Its Discovery to Clinical Trials and the Genomics Era
Jonathan D. Smith1  Qimin Hai1 
[1] Department of Cardiovascular & Metabolic Sciences, Cleveland Clinic, Cleveland, OH 44195, USA;
关键词: cholesterol esterification;    atherosclerosis;    ACAT;    SOAT;    inhibitors;    clinical trial;   
DOI  :  10.3390/metabo11080543
来源: DOAJ
【 摘 要 】

The purification and cloning of the acyl-coenzyme A: cholesterol acyltransferase (ACAT) enzymes and the sterol O-acyltransferase (SOAT) genes has opened new areas of interest in cholesterol metabolism given their profound effects on foam cell biology and intestinal lipid absorption. The generation of mouse models deficient in Soat1 or Soat2 confirmed the importance of their gene products on cholesterol esterification and lipoprotein physiology. Although these studies supported clinical trials which used non-selective ACAT inhibitors, these trials did not report benefits, and one showed an increased risk. Early genetic studies have implicated common variants in both genes with human traits, including lipoprotein levels, coronary artery disease, and Alzheimer’s disease; however, modern genome-wide association studies have not replicated these associations. In contrast, the common SOAT1 variants are most reproducibly associated with testosterone levels.

【 授权许可】

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