NDLI: PCSK9 inhibition and LDL cholesterol lowering: the biology of an attractive therapeutic target and critical review of the latest clinical trials

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Volume 13, 2018

Volume 12, 2017

Volume 11, 2016

Volume 10, 2015

Volume: 7 Issue: 7

Highlighting the future potential of PCSK9-targeted therapeutics

Management of dyslipidemia in HIV infection

PCSK9, a novel target for lowering LDL cholesterol: promise and progress

Endogenous sex hormones are associated with blood pressure change and hypertension incidence in postmenopausal women

PCSK9 inhibition and LDL cholesterol lowering: the biology of an attractive therapeutic target and critical review of the latest clinical trials

Investigating the pathogenesis and risk of Type 2 diabetes: clinical applications of metabolomics

Examining the role of lipid mediators in diabetic retinopathy

ABCA7: a potential mediator between cholesterol homeostasis and the host defense system

Treatment of hypercholesterolemia and hypertension in diabetics with coronary artery disease

Unraveling the role of nicotinamide phosphoribosyltransferase on lipids in atherosclerosis

Whole-blood viscosity and metabolic syndrome

An update on statin alternatives and adjuncts

Hypertriglyceridemia causes more severe course of acute pancreatitis

Reduction of LDL cholesterol by a monoclonal antibody to PCSK9 in rodents and nonhuman primates

Acknowledgements

Volume: 7 Issue: 6

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Volume: 7 Issue: 3

Volume: 7 Issue: 2

Volume: 7 Issue: 1

PCSK9 inhibition and LDL cholesterol lowering: the biology of an attractive therapeutic target and critical review of the latest clinical trials

Content Provider	Taylor & Francis Online
Author	Rhainds, David Tardif, Jean‑Claude Arsenault, Benoit J.
Abstract	PCSK9 is a serine protease expressed in the liver and the intestine. Gain-of-function mutations in PCSK9 are associated with autosomal dominant hypercholesterolemia, independently of mutations in apoB-100 or the LDL receptor (LDLR). Wild-type PCSK9 binds to the extracellular domain of the LDLR at the surface of hepatocytes, is internalized with the receptor and redirects it to lysosomes where the complex is degraded. Conversely, loss-of-function mutations in PCSK9 are associated with lower levels of LDL cholesterol (LDL-C) and reduced cardiovascular risk. Inhibition of PCSK9 binding to the LDLR with human monoclonal antibodies or reduction of PCSK9 expression with siRNA are the two main strategies to reduce LDL-C, which are actively pursued in the clinical development phases. In this article, the current evidence for PCSK9 as a target for reducing LDL-C and results of Phase I and II clinical trials with anti-PCSK9 therapeutic strategies are reviewed.
Starting Page	621
Ending Page	640
Page Count	20
File Format	PDF HTM / HTML
ISSN	17584299 17584302
Journal	Clinical Lipidology
Volume Number	7
Issue Number	6
DOI	10.2217/clp.12.74
Language	English
Publisher	Taylor & Francis
Publisher Date	2017-01-18
Access Restriction	Open
Subject Keyword	Familial hypercholesterolemia LDL receptor Monoclonal antibody PCSK9 SiRNA Statin
Content Type	Text
Subject	Endocrinology, Diabetes and Metabolism Cardiology and Cardiovascular Medicine

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