Fasting reduces plasma proprotein convertase, subtilisin/kexin type 9 and cholesterol biosynthesis in humans

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A proprotein convertase subtilisin/kexin type 9 neutralizing antibody reduces serum cholesterol in mice and nonhuman primates.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) regulates serum LDL cholesterol (LDL-C) by interacting with the LDL receptor (LDLR) and is an attractive therapeutic target for LDL-C lowering. We have generated a neutralizing anti-PCSK9 antibody, mAb1, that binds to an epitope on PCSK9 adjacent to the region required for LDLR interaction. In vitro, mAb1 inhibits PCSK9 binding to the LDLR a...

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Proprotein convertase substilisin/kexin type 9 antagonism reduces low-density lipoprotein cholesterol in statin-treated hypercholesterolemic nonhuman primates.

Proprotein convertase substilisin/kexin type 9 (PCSK9) promotes the degradation of low-density lipoprotein (LDL) receptor (LDLR) and thereby increases serum LDL-cholesterol (LDL-C). We have developed a humanized monoclonal antibody that recognizes the LDLR binding domain of PCSK9. This antibody, J16, and its precursor mouse antibody, J10, potently inhibit PCSK9 binding to the LDLR extracellular...

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Circulating proprotein convertase subtilisin kexin type 9 has a diurnal rhythm synchronous with cholesterol synthesis and is reduced by fasting in humans.

OBJECTIVE To gain insight into the function of proprotein convertase subtilisin kexin type 9 (PCSK9) in humans by establishing whether circulating levels are influenced by diurnal, dietary, and hormonal changes. METHODS AND RESULTS We monitored circulating PCSK9 in a set of dynamic human experiments and could show that serum PCSK9 levels display a diurnal rhythm that closely parallels that of...

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Rosuvastatin, proprotein convertase subtilisin/kexin type 9 concentrations, and LDL cholesterol response: the JUPITER trial.

BACKGROUND Although statin therapy is known to increase concentrations of PCSK9, whether this effect is related to the magnitude of LDL reduction is uncertain. This study was undertaken to understand the extent of this effect and examine the relationship between PCSK9 and LDL cholesterol (LDL-C) reduction. METHODS We measured plasma PCSK9 concentrations by ELISA at baseline and at 1 year in 5...

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Rosuvastatin, Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Concentrations, and LDL Cholesterol Response: the JUPITER Trial

METHODS: We measured plasma PCSK9 concentrations by ELISA at baseline and at 1 year in 500 men and 500 women participating in the Justification for Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) trial that randomly allocated participants to rosuvastatin 20 mg daily or placebo. We also evaluated rs11591147, a single nucleotide polymorphism known to have an ...

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ژورنال

عنوان ژورنال: Journal of Lipid Research

سال: 2010

ISSN: 0022-2275

DOI: 10.1194/jlr.p009860