Published in Human Genetics
Familial hypercholesterolemia results from mutations in the low-density lipoprotein (LDL) receptor or apolipoprotein B genes. We have previously reported the identification of a Utah autosomal-dominant hypercholesterolemia pedigree (kindred 1173) that did not show linkage to either of these loci (Hunt et al. 2000). Expansion of the pedigree and inc...
Published in Archives of Biochemistry and Biophysics
Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a critical role in cholesterol metabolism by enhancing the degradation of the LDL receptor protein in the liver. It has previously been shown that administration of zaragozic acid A (ZA), a potent inhibitor of squalene synthase, also significantly increases the rate of degradation of hepat...
Published in Biochemical and Biophysical Research Communications
Modulation of bile acid synthesis in human by cholestyramine or by chenodeoxycholic acid (CDCA) treatment affects lipoprotein metabolism leading to altered plasma lipid levels. The molecular changes caused by these treatments, which in turn influence lipoprotein metabolism, are still not entirely known in humans. In this study, mRNA levels were ana...
Published in Archives of Biochemistry and Biophysics
Since the hepatic LDL receptor is regarded as a major determinant of plasma LDL levels, the effect of diabetes on the expression of this receptor was examined in rat liver. Inducing diabetes with streptozotocin caused a significant reduction in hepatic LDL receptor mRNA levels in concert with an increase in serum cholesterol levels. However, LDL re...
Published in Annales d'Endocrinologie
Les gènes codant le récepteur des lipoprotéines de faible densité (LDLR) et son ligand l'apolipoprotéine B ont été longtemps les seuls incriminés dans l'hypercholestérolémie à transmission autosomique dominante (ADH). Nos travaux ont permis d'identifier en 2003, le troisième gène impliqué dans cette maladie : PCSK9, (Proprotéine Convertase Subtilis...
Published in Biochemical and Biophysical Research Communications
Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a serine protease that is known to reduce hepatic low-density lipoprotein receptor (LDLR) levels and increase plasma LDL cholesterol. It is not clear, however, whether secreted PCSK9 degrades extrahepatic LDLRs. We present evidence that recombinant PCSK9, either injected intravenously into or...
Published in Biochemical and Biophysical Research Communications
Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to low density lipoprotein receptor (LDLR) and induces its internalization and degradation. PCSK9 binding to LDLR is mediated through the LDLR epidermal growth factor-like repeat A (EGF-A) domain. We show for the first time that an EGF-A peptide inhibits PCSK9-mediated degradation of LDLR ...
Published in Pharmacogenetics and genomics
The authors' findings suggest that evolutionary dynamics may underlie the 'gain-of-function' mutations in PCSK9 that are associated with higher LDL cholesterol levels.
Published in Atherosclerosis
Background We hypothesized that variants in PCSK9 that lower LDL cholesterol levels are associated with reduced prevalence and incidence of peripheral artery disease (PAD). Methods The Atherosclerosis Risk in Communities (ARIC) Study assessed risk factors and PCSK9 variants Y142X and C679X (relevant to blacks) and R46L (relevant to whites) in a coh...
Published in EMBO reports
We have recently identified a new form of post-translational regulation of BACE1 (beta-site amyloid precursor protein (APP)-cleaving enzyme 1), a membrane protein that acts as the rate-limiting enzyme in the generation of the Alzheimer disease amyloid beta-peptide (Abeta). Specifically, BACE1 is transiently acetylated on seven lysine residues in th...
