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首页> 外文期刊>Current opinion in lipidology >And then there were acyl coenzyme A: cholesterol acyl transferase inhibitors.
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And then there were acyl coenzyme A: cholesterol acyl transferase inhibitors.

机译：然后是酰基辅酶A：胆固醇酰基转移酶抑制剂。

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PURPOSE OF REVIEW: The reputation of acyl coenzyme A:cholesterol acyltransferase (ACAT) inhibitors has changed profoundly from promising new drugs for cardiovascular prevention to drugs without clinical benefits or possibly even with adverse effects. RECENT FINDINGS: ACAT inhibitors decrease the intracellular conversion of free cholesterol into cholesteryl ester in a number of tissues, including intestine, liver and macrophages. In contrast to promising results in experimental animal models, all subsequent clinical studies in humans with ACAT inhibitors failed to show lipid profile changes as well as reductions in surrogate markers for coronary artery disease. In fact, there was even a tendency towards an increase in atheroma burden in the most recent and well executed clinical trials. In addition, the inhibition of this pivotal enzyme in cholesterol esterification may interfere with reverse cholesterol transport. SUMMARY: In our opinion, the consistent negative findings in recent clinical trials have virtually eliminated the chances for this class of drugs to be introduced for cardiovascular prevention. Possible strategies focused on selective ACAT 2 inhibition or the combination of ACAT inhibitors with compounds that stimulate reverse cholesterol transport may prove to have clinical benefit. This will have to await further clinical research in humans, however, as, obviously, rodent models cannot provide reliable data as to the efficacy of this class of drugs in humans.
机译：审查的目的：酰基辅酶A：胆固醇酰基转移酶（ACAT）抑制剂的声誉已从有前途的心血管预防新药变为无临床益处甚至可能有不良反应的药物。最近的发现：ACAT抑制剂可降低肠道，肝脏和巨噬细胞等许多组织中游离胆固醇向胆固醇酯的细胞内转化。与实验动物模型中令人鼓舞的结果相反，所有随后使用ACAT抑制剂进行的人类临床研究均未显示脂质分布变化以及冠状动脉疾病的替代标志物减少。实际上，在最新且执行良好的临床试验中，甚至有增加动脉粥样硬化负担的趋势。此外，在胆固醇酯化中抑制这种关键酶可能会干扰胆固醇的逆向转运。简介：我们认为，近期临床试验中一致的阴性结果实际上消除了将此类药物引入心血管预防的机会。集中于选择性抑制ACAT 2或将ACAT抑制剂与刺激胆固醇反向转运的化合物结合使用的可能策略可能证明具有临床益处。这将有待人类进一步的临床研究，但是，显然，啮齿动物模型无法提供有关此类药物在人类中的功效的可靠数据。

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