Costet Philippe, Krempf Michel, Cariou Bertrand
INSERM, UMR915, L'Institut du Thorax, 1 Rue Gaston Veil, Nantes, France.
Trends Biochem Sci. 2008 Sep;33(9):426-34. doi: 10.1016/j.tibs.2008.06.005. Epub 2008 Jul 30.
Gain-of-function mutations within proprotein convertase subtilisin kexin type 9 (PCSK9) are linked to familial autosomal dominant hypercholesterolaemia, a disease characterized by elevated plasma concentrations of cholesterol associated with low-density lipoproteins (LDLs). Conversely, PCSK9 loss-of-function mutations result in low levels of LDL cholesterol (LDLC) and protect against coronary heart disease. Although compelling evidence indicates that PCSK9 impairs the LDLR pathway, its role in cholesterol metabolism remains incompletely defined. In the past two years, several new biochemical findings, including the PCSK9 crystal structure and the identification of several transcriptional repressors, were reported. Moreover, new clinical and epidemiological data have revealed the correlation between plasma PCSK9 concentrations and LDLC levels.
前蛋白转化酶枯草溶菌素9型（PCSK9）的功能获得性突变与家族性常染色体显性高胆固醇血症相关，该疾病的特征是与低密度脂蛋白（LDL）相关的血浆胆固醇浓度升高。相反，PCSK9功能丧失性突变导致低密度脂蛋白胆固醇（LDLC）水平降低，并预防冠心病。尽管有力证据表明PCSK9会损害低密度脂蛋白受体（LDLR）途径，但其在胆固醇代谢中的作用仍未完全明确。在过去两年中，报道了多项新的生化研究结果，包括PCSK9晶体结构以及几种转录抑制因子的鉴定。此外，新的临床和流行病学数据揭示了血浆PCSK9浓度与LDLC水平之间的相关性。
