PCSK9的生物学相关性:当越少越好....

M. Mbikay, M. Chrétien
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引用次数: 2

摘要

蛋白转化酶Subtilisin/Kexin-type 9 (PCSK9)是肝脏低密度脂蛋白受体(LDLR)的循环负调节因子,可清除血液中的胆固醇。增强PCSK9活性的功能获得性基因突变已被发现可导致潜在致命性的家族性高胆固醇血症。相反,通过基因功能丧失或药物减少其活性可增加肝脏LDLR,降低血液胆固醇,并预防心血管疾病。新的流行病学和实验证据表明,这种减少也可以减轻炎症,增强癌症免疫,提供抗感染能力,并防止肝脏病变。在这篇综述中,我们质疑该蛋白在正常生理下的相关性。我们认为PCSK9是胆固醇代谢和免疫的重要但非必需的调节剂,其致病性源于其慢性过表达。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The Biological Relevance of PCSK9: When Less Is Better….
Proprotein Convertase Subtilisin/Kexin-type 9 (PCSK9) is a circulating negative regulator of hepatic low-density lipoprotein receptor (LDLR) which clears cholesterol from blood. Gain-of-function genetic mutations which amplify PCSK9 activity have been found to cause potentially lethal familial hypercholesterolemia. Inversely, reduction of its activity through loss-of-function genetics or with pharmaceuticals was shown to increase hepatic LDLR, to lower blood cholesterol, and to protect against cardiovascular diseases. New epidemiological and experimental evidence suggests that this reduction could also attenuate inflammation, reinforce cancer immunity, provide resistance to infections, and protect against liver pathologies. In this review, we question the relevance of this protein under normal physiology. We propose that PCSK9 is an important, but non-essential, modulator of cholesterol metabolism and immunity, and that its pathogenicity results from its chronic overexpression.
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