Search results for "Proprotein Convertase 9"
showing 10 items of 36 documents
Proprotein Convertase Subtilisin Kexin Type 9 Inhibition for Autosomal Recessive Hypercholesterolemia—Brief Report
2016
Objective— Proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors lower low-density lipoprotein (LDL) cholesterol in the vast majority of patients with autosomal dominant familial hypercholesterolemia. Will PCSK9 inhibition with monoclonal antibodies, in particular alirocumab, be of therapeutic value for patients with autosomal recessive hypercholesterolemia (ARH)? Approach and Results— Primary lymphocytes were obtained from 28 genetically characterized ARH patients and 11 controls. ARH lymphocytes treated with mevastatin were incubated with increasing doses of recombinant PCSK9 with or without saturating concentrations of alirocumab. Cell surface LDL receptor expression measured…
Next-generation-sequencing-based identification of familial hypercholesterolemia-related mutations in subjects with increased LDL–C levels in a latvi…
2015
Background Familial hypercholesterolemia (FH) is one of the commonest monogenic disorders, predominantly inherited as an autosomal dominant trait. When untreated, it results in early coronary heart disease. The vast majority of FH remains undiagnosed in Latvia. The identification and early treatment of affected individuals remain a challenge worldwide. Most cases of FH are caused by mutations in one of four genes, APOB, LDLR, PCSK9, or LDLRAP1. The spectrum of disease-causing variants is very diverse and the variation detection panels usually used in its diagnosis cover only a minority of the disease-causing gene variants. However, DNA-based tests may provide an FH diagnosis for FH patients…
Cardiovascular Efficacy and Safety of Bococizumab in High-Risk Patients
2017
Item does not contain fulltext BACKGROUND: Bococizumab is a humanized monoclonal antibody that inhibits proprotein convertase subtilisin-kexin type 9 (PCSK9) and reduces levels of low-density lipoprotein (LDL) cholesterol. We sought to evaluate the efficacy of bococizumab in patients at high cardiovascular risk. METHODS: In two parallel, multinational trials with different entry criteria for LDL cholesterol levels, we randomly assigned the 27,438 patients in the combined trials to receive bococizumab (at a dose of 150 mg) subcutaneously every 2 weeks or placebo. The primary end point was nonfatal myocardial infarction, nonfatal stroke, hospitalization for unstable angina requiring urgent re…
The c.43_44insCTG variation in PCSK9 is associated with low plasma LDL-cholesterol in a Caucasian population.
2006
Abstract The genetic etiology of familial hypobetalipoproteinemia (FHBL) is unclear in the majority of cases. Mutations in apolipoprotein B (APOB) are the only confirmed causes of FHBL. Recently, loss-of-function mutations of PCSK9 gene have been shown to be associated with the hypocholesterolemia phenotype. Our primary goal was to confirm that mutations in PCSK9 could be another cause of FHBL. Using the sequencing approach, we found that the c.43_44insCTG variation in PCSK9, a common in-frame insertion in both African American and Caucasian populations, is associated with the hypocholesterolemia phenotype in three FHBL families. Then we tested whether this variation could be associated wit…
Global perspective of familial hypercholesterolaemia: a cross-sectional study from the EAS Familial Hypercholesterolaemia Studies Collaboration (FHSC)
2021
Background The European Atherosclerosis Society Familial Hypercholesterolaemia Studies Collaboration (FHSC) global registry provides a platform for the global surveillance of familial hypercholesterolaemia through harmonisation and pooling of multinational data. In this study, we aimed to characterise the adult population with heterozygous familial hypercholesterolaemia and described how it is detected and managed globally. Methods Using FHSC global registry data, we did a cross-sectional assessment of adults (aged 18 years or older) with a clinical or genetic diagnosis of probable or definite heterozygous familial hypercholesterolaemia at the time they were entered into the registries. Dat…
PCSK9 rs11591147 R46L loss-of-function variant protects against liver damage in individuals with NAFLD
2020
Background and Aims: The proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a key role in cholesterol homeostasis, and its inhibition represents an effective therapy to lower low-density lipoprotein cholesterol (LDL-C) levels. In this study, we examined the impact of the PCSK9 rs11591147 loss-of-function (LOF) variant on liver damage in a multicenter collection of patients at risk of nonalcoholic steatohepatitis (NASH), in clinical samples and experimental models. Methods: We considered 1874 consecutive individuals at risk of NASH as determined by histology. The SNP rs11591147, encoding for the p.R46L variant of PCSK9, was genotyped by TaqMan assays. We also evaluated 1) PCSK9 mRNA…
Role of PCSK9 in the course of ejection fraction change after ST-segment elevation myocardial infarction: a pilot study
2020
Altres ajuts: Conselleria d'Educació, Investigació, Cultura i Esport GV/2018/116 Proprotein convertase subtilisin/kexin type 9 (PCSK9) has emerged as a therapeutic target for reducing plasma low-density lipoprotein cholesterol. Beyond lipid control, recent findings suggest a deleterious effect of this protein in the pathogenesis of postmyocardial infarction left ventricle remodelling and heart failure-related complications. The aim of this study was to assess the relationship between circulating PCSK9 and 6 month cardiac magnetic resonance imaging-derived left ventricular ejection fraction (LVEF) after a first ST-segment elevation myocardial infarction (STEMI). We prospectively evaluated 40…
Real-world study: Escalating targeted lipid-lowering treatment with PCSK9-inhibitors and lipoprotein apheresis.
2018
INTRODUCTION Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition with monoclonal antibodies has complemented the armamentarium of lipid-lowering therapy (LLT) before the final step of commencing chronic lipoprotein apheresis (LA). Data are scarce on patients who, after escalation of LLT with PCSK9 antibodies, have commenced chronic LA or PCSK9 antibody treatment during ongoing long-term LA. PATIENTS AND METHODS In this study, a cohort of 110 patients with established atherosclerotic cardiovascular disease (ASCVD) due to hypercholesterolemia or concomitant lipoprotein(a)-hyperlipoproteinemia, who received PCSK9 antibodies for the first time during routine care, were consecutivel…
PCSK9 Confers Inflammatory Properties to Extracellular Vesicles Released by Vascular Smooth Muscle Cells
2022
Vascular smooth muscle cells (VSMCs) are key participants in both early- and late-stage atherosclerosis and influence neighbouring cells possibly by means of bioactive molecules, some of which are packed into extracellular vesicles (EVs). Proprotein convertase subtilisin/kexin type 9 (PCSK9) is expressed and secreted by VSMCs. This study aimed to unravel the role of PCSK9 on VSMCs-derived EVs in terms of content and functionality. EVs were isolated from human VSMCs overexpressing human PCSK9 (VSMCPCSK9-EVs) and tested on endothelial cells, monocytes, macrophages and in a model of zebrafish embryos. Compared to EVs released from wild-type VSMCs, VSMCPCSK9-EVs caused a rise in the expression …
The Impact of the International Cooperation On Familial Hypercholesterolemia Screening and Treatment: Results from the ScreenPro FH Project
2019
Purpose of Review Familial hypercholesterolemia (FH) is often perceived and described as underdiagnosed and undertreated, though effective treatment of FH is available. Owing to the mentioned facts, it is ever more imperative to screen and treat FH patients. Subsequent to the identification of patients, the project focuses on the improvement of their prognoses. The ScreenPro FH project was established as a functional international network for the diagnosis, screening, and treatment of FH. Individual countries were assigned goals, e.g., to define the actual situation and available treatment. With “central support,” more centers and countries participated in the project. Subsequently, individ…