Acyl-Coenzyme A: Cholesterol Acyltransferase (ACAT) in Cholesterol Metabolism: From Its Discovery to Clinical Trials and the Genomics Era.
Acyl-Coenzyme A: Cholesterol Acyltransferase (ACAT) in Cholesterol Metabolism: From Its Discovery to Clinical Trials and the Genomics Era.
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DOI：
10.3390/metabo11080543
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发表时间：
2021-08-14
期刊：
影响因子：
4.1
通讯作者：
Smith JD
中科院分区：
文献类型：
--
作者：
Hai Q;Smith JD
酰基辅酶A：胆固醇酰基转移酶（ACAT）和甾醇O-酰基转移酶（SOAT）基因的纯化和克隆开辟了胆固醇代谢的新领域，因为它们对泡沫细胞生物学和肠道脂质吸收有深远的影响。Soat 1或Soat 2缺陷小鼠模型的产生证实了其基因产物对胆固醇酯化和脂蛋白生理学的重要性。尽管这些研究支持使用非选择性ACAT抑制剂的临床试验，但这些试验并未报告获益，其中一项试验显示风险增加。早期的遗传学研究表明，这两种基因的共同变异与人类特征有关，包括脂蛋白水平、冠状动脉疾病和阿尔茨海默病;然而，现代全基因组关联研究并没有复制这些关联。相比之下，常见的SOAT 1变体与睾酮水平的相关性最高。
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.
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