The present study aimed to examine the impact of introducing stable liver transduction of human derived PCSK9 with a gain of function D374Y mutation (PCSK9) into systemic PPARα knockout mice (PPARα) on plasma lipid levels and AS. Enzymatic assays were employed to evaluate plasma lipid ...
PCSK9(前蛋白转化酶枯草溶菌素9)是科学界和制药界的传奇靶点,PCSK9由肝细胞产生后分泌到血液中,与低密度脂蛋白LDLR结合介导其降解。2003年被法国科学家Abifadel et al. 首次报道,在一个法国家庭中PCSK9的功能获得性突变(gain-of-function mutation)导致家族性高胆固...
PCSK9(前蛋白转化酶枯草溶菌素9)是科学界和制药界的传奇靶点,PCSK9由肝细胞产生后分泌到血液中,与低密度脂蛋白LDLR结合介导其降解。2003年被法国科学家Abifadel et al. 首次报道,在一个法国家庭中PCSK9的功能获得性突变(gain-of-function mutation)导致家族性高胆固醇血症,该遗传特征是单基因显性遗传。 该发现导致...
One of the "gain-of-function" mutants, PCSK9-S127R, which has impaired autocatalytic activity, is defective in binding to c-IAP1. The other dominant mutation, PCSK9-D374Y^12^, which is 10-fold more potent in degrading the LDLR protein than wild-type PCSK9, can be significantly ...
Infusion of PCSK9(D374Y), a gain-of-function mutation, resulted in accelerated clearance of the mutant PCSK9 and a greater reduction in hepatic LDLRs. Combined, these data suggest that exogenously administrated PCSK9 in plasma preferentially reduces LDLR protein levels in liver at concentrations ...
Gain-of-function mutations in PCSK9 are associated with familial hypercholesterolemia, whereas loss-of-function mutations are protective against ASCVD. Therefore, PCSK9 inhibition offers a promising supplement or alternative to statin therapy in the reduction of LDL-C. Numerous phase II and III ...
Mutations which increase the activity of PCSK9 towards the LDLR are referred to as gain-of-function mutations and these mutations cause autosomal dominant hypercholesterolemia. Mutations which decrease the activity of PCSK9 are referred to as loss-of-function mutations and these mutations cause ...
Inbred lines increased the consistency of the genetic background of the experimental animals, thus consequently, would simplify disease progression of the animal model. This study used Wuzhishan minipig intending to make a transgenic pig with gain-of-function D374Y mutation of human PCSK9, and to...
Genome-wide expression analysis of cells expressing gain of function mutant D374Y-PCSK9. J Cell Physiol. 2008;217(2):459–67. https://doi.org/10.1002/jcp.21519. Article CAS PubMed Google Scholar Mbikay M, Sirois F, Mayne J, Wang GS, Chen A, Dewpura T, Prat A, Seidah NG, C...
However, PCSK9 has two types of mutations, gain-of-function mutations and loss-of-function mutations. Population studies have shown that several “gain-of-function” mutations of PCSK9 often occur in individuals with autosomal dominant hypercholesterolemia, while “loss-of-function” mutations of ...