Millán Núñez-Cortés Jesús, Mostaza Prieto José M
Unidad de Lípidos y Riesgo Vascular, Hospital General Universitario Gregorio Marañón, Madrid, España.
Unidad de Lípidos, Servicio de Medicina Interna, Hospital Carlos III, Madrid, España.
Clin Investig Arterioscler. 2016 May;28 Suppl 2:9-13. doi: 10.1016/S0214-9168(16)30165-6.
PCSK9 is a protease, synthesized mainly in the liver, which promotes the hepatic degradation of the LDL receptor and consequently decreases LDL receptor density and clearance of LDL particles. Statins inhibit HMG-CoA-reductase activity, an enzyme that catalyses an important step in hepatic cholesterol biosynthesis. The decrease of the hepatic intracellular cholesterol pool produced by these drugs upregulates the activity of the SREBP2 transcription factor, which subsequently stimulates the expression of the LDL receptor gene, an effect that is followed by an increase in the serum concentration of PCSK9. This article aims to review the effects of different lipid-lowering drugs on plasma PCSK9 concentrations. Overall, statins increase blood PCSK9 levels, an effect that is enhanced by ezetimibe. In contrast, others drugs, such as fibrates and niacin, could decrease PCSK9 levels.
前蛋白转化酶枯草溶菌素9(PCSK9)是一种主要在肝脏合成的蛋白酶,它会促进低密度脂蛋白(LDL)受体的肝脏降解,从而降低LDL受体密度以及LDL颗粒的清除率。他汀类药物抑制3-羟基-3-甲基戊二酰辅酶A(HMG-CoA)还原酶的活性,该酶催化肝脏胆固醇生物合成中的一个重要步骤。这些药物导致肝脏细胞内胆固醇池减少,从而上调固醇调节元件结合蛋白2(SREBP2)转录因子的活性,随后刺激LDL受体基因的表达,这一效应之后会伴随着PCSK9血清浓度升高。本文旨在综述不同降脂药物对血浆PCSK9浓度的影响。总体而言,他汀类药物会升高血液中PCSK9水平,依折麦布会增强这一效应。相比之下,其他药物,如贝特类药物和烟酸,可能会降低PCSK9水平。