Search results for "PCS"
showing 10 items of 94 documents
A new PCSK9 gene promoter variant affects gene expression and causes autosomal dominant hypercholesterolemia.
2008
Autosomal dominant hypercholesterolemia (ADH) is a genetic disorder characterized by increased low-density lipoprotein (LDL)-cholesterol levels, leading to high risk of premature cardiovascular disease. More than 900 mutations in LDL receptor, six in APOB and 10 in PCSK9 have been identified as a cause of the disease in different populations. All known mutations in PCSK9 causing hypercholesterolemia produce an increase in the enzymatic activity of this protease. Up to now, there are data about the implication of PCSK9 in ADH in a low number of populations, not including a Spanish population.The objective of the study was to study the prevalence of PCSK9 mutations in ADH Spanish population.W…
Spectrum of mutations and phenotypic expression in patients with autosomal dominant hypercholesterolemia identified in Italy.
2013
Abstract Objective To determine the spectrum of gene mutations and the genotype–phenotype correlations in patients with Autosomal Dominant Hypercholesterolemia (ADH) identified in Italy. Methods The resequencing of LDLR , PCSK9 genes and a selected region of APOB gene were conducted in 1018 index subjects clinically heterozygous ADH and in 52 patients clinically homozygous ADH. The analysis was also extended to 1008 family members of mutation positive subjects. Results Mutations were detected in 832 individuals: 97.4% with LDLR mutations, 2.2% with APOB mutations and 0.36% with PCSK9 mutations. Among the patients with homozygous ADH, 51 were carriers of LDLR mutations and one was an LDLR / …
Effects of PCSK9 variants on common carotid artery intima media thickness and relation to ApoE alleles.
2009
BACKGROUND: PCSK9 plays a key role in plasma cholesterol metabolism by modulating the expression of LDL receptors. OBJECTIVE AND METHODS: In this study we investigated the effects of two common polymorphism of the PCSK9 gene (E670G and I474V) on the intima media thickness of the common carotid artery and the possible relation with polymorphisms of apolipoprotein E in 1541 middle aged subjects selected from the general population enrolled in the PLIC study and confirmed the major findings in a second free-living population enrolled in the Ventimiglia study. RESULTS: 670G carriers showed significantly increased plasma total cholesterol, LDL-cholesterol, and Apo levels B while no significant d…
Reduced VLDL clearance in ApoeNpc1 mice is associated with increased Pcsk9 and Idol expression and decreased hepatic LDL-receptor levels
2010
Niemann-Pick type C1 (NPC1) promotes the transport of LDL receptor (LDL-R)-derived cholesterol from late endosomes/lysosomes to other cellular compartments. NPC1-deficient cells showed impaired regulation of liver_X receptor (LXR) and sterol regulatory element-binding protein (SREBP) target genes. We observed that Apoe(-/-)Npc1(-/-) mice displayed a marked increase in total plasma cholesterol mainly due to increased VLDL, reflecting decreased clearance. Although nuclear SREBP-2 and Ldlr mRNA levels were increased in Apoe(-/-)Npc1(-/-) liver, LDL-R protein levels were decreased in association with marked induction of proprotein convertase subtilisin/kexin type 9 (Pcsk9) and inducible degrade…
Notch 1 pathway and EPCs in bicuspid aortic valve: is their interplay involved in the ascending aortic aneurysm onset?
2018
Backgroud_AIM: Bicuspid aortic valve (BAV) is frequently associated with development of ascending aortic aneurysm, even if the underlying mechanisms remain to be clarified. Here, we investigated if a deregulation of Notch1 signaling pathway and endothelial progenitor cells (EPCs) number is associated with BAV disease and an early ascending aortic aneurysm (AAA) onset. Methods: To this aim,70 subjects with BAV (M/F 50/20; mean age: 58.8±14.8 years) and 70 subjects with tricuspid aortic valve (TAV)(M/F 35/35; mean age: 69.1±12.8 years), AAA complicated or not, were enrolled. Multiparametric flow cytometry analyses, plasma amount assessments, gene expressions, and tissue protein semiquantitati…
Familial hypercholesterolæmia in children and adolescents: Gaining decades of life by optimizing detection and treatment
2015
Contains fulltext : 155263.pdf (Publisher’s version ) (Open Access) Familial hypercholesterolaemia (FH) is a common genetic cause of premature coronary heart disease (CHD). Globally, one baby is born with FH every minute. If diagnosed and treated early in childhood, individuals with FH can have normal life expectancy. This consensus paper aims to improve awareness of the need for early detection and management of FH children. Familial hypercholesterolaemia is diagnosed either on phenotypic criteria, i.e. an elevated low-density lipoprotein cholesterol (LDL-C) level plus a family history of elevated LDL-C, premature coronary artery disease and/or genetic diagnosis, or positive genetic testin…
Inclisiran: a small interfering RNA strategy targeting PCSK9 to treat hypercholesterolemia
2022
Introduction: Inclisiran is a novel posttranscriptional gene silencing therapy that inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9) synthesis by RNA interference and has a potent, dose-dependent, durable effect in lowering LDL-C, and therefore is an effective drug to treat dyslipidemia, reducing the risk for acute cardiovascular (CV) events. It is safe and well-tolerated. Areas covered: This paper aims to review the mechanism of action of inclisiran while evaluating its efficacy and safety in the treatment of dyslipidemia from data of the clinical trials in the ORION program. Expert opinion: Data from the clinical trials in the ORION program demonstrated efficacy and safety o…
Lomitapide does not alter PCSK9 and Lp(a) levels in homozygous familial hypercholesterolemia patients: analysis on cytokines and lipid profile
2021
Abstract Lomitapide, a drug for the treatment of homozygous familial hypercholesterolemia patients, reduced total and LDL cholesterol but no significant changes were observed on PCSK9 and Lp(a) plasma levels. Some changes of inflammatory mediators were also observed, including hsCRP, which may suggest an anti-inflammatory effect.
Insight into the Evolving Role of PCSK9
2022
Proprotein convertase subtilisin/kexin type 9 (PCSK9) is the last discovered member of the family of proprotein convertases (PCs), mainly synthetized in hepatic cells. This serine protease plays a pivotal role in the reduction of the number of low-density lipoprotein receptors (LDLRs) on the surface of hepatocytes, which leads to an increase in the level of cholesterol in the blood. This mechanism and the fact that gain of function (GOF) mutations in PCSK9 are responsible for causing familial hypercholesterolemia whereas loss-of-function (LOF) mutations are associated with hypocholesterolemia, prompted the invention of drugs that block PCSK9 action. The high efficiency of PCSK9 inhibitors (…
The European DEMO fusion reactor: Design status and challenges from balance of plant point of view
2017
DEMO initial conceptual design studies are being conducted in Europe as part of the European Union Roadmap to Fusion Electricity, which aims to demonstrate the feasibility of electricity produced by nuclear fusion reactors around the middle of this century. The aim of this paper is to provide an overview of the DEMO project, highlighting its main characteristics and challenges in terms of design, integration, and operation. Particular emphasis is given on some important systems of the Balance of Plant (BoP), such as the primary heat transfer systems, the related power conversion systems, and the electrical power plant. The relevance of such systems is due to the need of a continuous reanaly…