K08653 MBTPS1; membrane-bound transcription factor site-1 protease [EC:3.4.21.112] K01349 FURIN; furin [EC:3.4.21.75] K01359 PCSK1; proprotein convertase subtilisin/kexin type 1 [EC:3.4.21.93] K01360 PCSK2; proprotein convertase subtilisin/kexin type 2 [EC:3.4.21.94] K08671 PCSK4; proprotein convertase subtilisin/kexin type 4 [EC:3.4.21.-] K08654 PCSK5; proprotein convertase subtilisin/kexin type 5 [EC:3.4.21.-] K08654 PCSK5; proprotein convertase subtilisin/kexin type 5 [EC:3.4.21.-] K08672 PCSK6; proprotein convertase subtilisin/kexin type 6 [EC:3.4.21.-] K08673 PCSK7; proprotein convertase subtilisin/kexin type 7 [EC:3.4.21.-] K08673 PCSK7; proprotein convertase subtilisin/kexin type 7 [EC:3.4.21.-] K13050 PCSK9; proprotein convertase subtilisin/kexin type 9 [EC:3.4.21.-] K01280 TPP2; tripeptidyl-peptidase II [EC:3.4.14.10 ...
K08653 MBTPS1; membrane-bound transcription factor site-1 protease [EC:3.4.21.112] K01349 FURIN; furin [EC:3.4.21.75] K01359 PCSK1; proprotein convertase subtilisin/kexin type 1 [EC:3.4.21.93] K01360 PCSK2; proprotein convertase subtilisin/kexin type 2 [EC:3.4.21.94] K08654 PCSK5; proprotein convertase subtilisin/kexin type 5 [EC:3.4.21.-] K08672 PCSK6; proprotein convertase subtilisin/kexin type 6 [EC:3.4.21.-] K08673 PCSK7; proprotein convertase subtilisin/kexin type 7 [EC:3.4.21.-] K13050 PCSK9; proprotein convertase subtilisin/kexin type 9 [EC:3.4.21.-] K01280 TPP2; tripeptidyl-peptidase II [EC:3.4.14.10 ...
Proprotein Convertase Subtilisin/Kexin Type 9 (Proprotein Convertase 9 or Neural Apoptosis-Regulated Convertase 1 or PCSK9 or EC 3.4.21.) - Pipeline Review, H1 2016 Proprotein Convertase - Market research report and industry analysis - 10197474
Proprotein convertase subtilisin/kexin type 9 (PCSK9) regulates LDL cholesterol metabolism by targeting LDL receptors for degradation. Statins increase serum PCSK9 concentration limiting the potential of statins to reduce LDL cholesterol, whereas ezetimibe, inhibitor of cholesterol absorption, has ambiguous effects on circulating PCSK9 levels. Plant stanols also reduce cholesterol absorption, but their effect on serum PCSK9 concentration is not known. Therefore, we performed a controlled, randomized, double-blind study, in which 92 normo- to moderately hypercholesterolemic subjects (35 males and 57 females) consumed vegetable-oil spread 20 g/d enriched (plant stanol group, n=46) or not (control group, n=46) with plant stanol 3g/d as ester for 6 months. Fasting blood samples were drawn at baseline and at the end of the study. Serum PCSK9 concentration was analyzed with Quantikine Elisa Immunoassay, serum and lipoprotein lipids enzymatically, and serum non-cholesterol sterols with gas-liquid ...
We read with interest the article by Rashid and colleagues1 in Circulation in which they studied the physiological role of proprotein convertase subtilisin/kexin type 9 (PCSK9) in intestinal triglyceride-rich lipoprotein production. In that article, Rashid et al stated that few investigators have characterized the functional importance of PCSK9 in the small intestine and its regulatory role on triglyceride-rich lipoprotein metabolism.1 However, they omitted 2 seminal articles that previously addressed the question.. We demonstrated and published in 2009 in Arteriosclerosis, Thrombosis, and Vascular Biology that PCSK9-deficient mice display reduced postprandial hypertriglyceridemia after an olive oil gavage.2 Using the lymph duct cannulation method, we also showed that PCSK9-deficient mice have reduced intestinal apolipoprotein B production compared with wild-type mice.2 Finally, we confirmed this relationship between intestinal PCSK9 and apolipoprotein B secretion in vitro in differentiated ...
... , Authors: Dessen P. Published in: Atlas Genet Cytogenet Oncol Haematol.
The mature PCSK9 binds with LDLR protein to form a complex to direct LDLR protein toward lysosome for degradation. Thus, PCSK9 inhibits LDLR expression at a post-transcriptional level and plays a critical role in cholesterol homeostasis.23 In addition to SREBP2, we have reported that PPARγ is another transcription factor activating PCSK9 transcription because a PPRE exists in the PCSK9 promoter.24 In the current study, at cellular levels, we determined that PCSK9 expression can be induced by AdipoR agonists, and the induction was completed by activating PPARγ pathway. The induction of PCSK9 expression/secretion was also observed in wild-type mice. Meanwhile, AdipoR agonists activated SRE in the promoter of LDLR, but not of PCSK9, which resulted in a direct induction of LDLR expression by AdipoR agonists and surpassed the facilitation of LDLR degradation by increased PCSK9. Therefore, the long-term ADP355 treatment decreased serum total and LDL-C levels, but increased apoE levels in wild-type ...
Proprotein convertase involved in the processing of hormone and other protein precursors at sites comprised of pairs of basic amino acid residues (By similarity). In males, important for ADAM2 processing as well as other acrosomal proteins with roles in fertilization and critical for normal fertilization events such as sperm capacitation, acrosome reaction and binding of sperm to zona pellucida (By similarity). Plays also a role in female fertility, involved in the regulation of trophoblast migration and placental development, may be through the proteolytical processing and activation of proteins such as IGF2 (PubMed:16040806). May also participate in folliculogenesis in the ovaries (By similarity).
Introduction: CAT-2003 is an orally active small molecule that inhibits SREBP maturation (nSREBP-1 and nSREBP-2) and activation of SREBP-target genes, including PCSK9. CAT-2003 mechanism of action was studied in HepG2 cells and in the transgenic ApoE*3 Leiden mouse model of hyperlipoproteinemia.. Methods and Results: In vitro, CAT-2003 was studied in HepG2 cells and dose dependently reduced mature SREBP-2 protein levels (50% at 25 μM, n=3), PCSK9 mRNA (IC50 16.2 +/- 1.1 μM, n=3), and PCSK9 protein secretion (IC50 = 17.8 +/- 1.1 μM, n=3). CAT-2003 treatment also reduced expression of other SREBP target genes as well as SREBP processing genes including those encoding for HMG-CoA reductase, SCD-1, ACC2, S1P and S2P proteins. The reduction in PCSK9 protein correlated dose dependently with an increase in both low and high molecular weight LDLR protein. Statins increase nSREBP-2 and increase the production of PCSK9. CAT-2003 reversed atorvastatin-induced increases in nSREBP-2 and PCSK9 production ...
We examine the secondary preventive effect of acute phase use of PCSK9 inhibitors after coronary intervention in patients with acute myocardial infarction.
Reaktivität: Fledermaus, Huhn, Rind (Kuh) and more. 63 verschiedene PCSK2 Antikörper vergleichen. Alle direkt auf antikörper-online bestellbar!
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sp:NEC1_MOUSE] Pcsk1, Nec-1, Nec1, PC1, PC3, Phpp-1, SPC3; proprotein convertase subtilisin/kexin type 1; K01359 proprotein convertase subtilisin/kexin type 1 [EC:3.4.21.93] ...
sp:NEC1_MOUSE tr:Q32MU0_MOUSE] Pcsk1, Nec-1, Nec1, PC1, PC3, Phpp-1, SPC3; proprotein convertase subtilisin/kexin type 1; K01359 proprotein convertase subtilisin/kexin type 1 [EC:3.4.21.93] ...
A total of 406 participants were randomized to the AMG 145 treatment arms, placebo arms, and the ezetimibe arm, with approximately 45 participants per arm. The mean age of the patients was 51 years, 34% were men, and 79% were white. Mean LDL-C concentration at baseline was 3.7 mmol/L. Of the patients enrolled, 21% of patients had two or more cardiovascular risk factors, 32% had metabolic syndrome, and no one had a history of coronary artery disease. AMG 145 significantly reduced LDL-C concentrations in all dose groups. The changes from baseline were -41.0% (95% confidence interval -46.2 to -35.8) for the AMG 70 mg/2-week dose; -43.9% (-49.0 to -38.7) for the 105 mg/2-week dose; and -50.9% (-56.2 to -45.7) for the 140 mg/2-week dose. Doses given every 4 weeks also resulted in reduced LDL-C. The changes from baseline were -39.0% (-44.1 to -34.0) for the 280 mg/4-week dose; -43.2% (-48.3 to -38.1) for the 350 mg/4-week dose; and -48.0% (-53.1 to -42.9) for the 420 mg/4-week dose. The placebo groups ...
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The FDA recently announced approval of two cholesterol lowering drugs which both work by inhibiting PCSK9 or proprotein convertase subtilisin/kexin type 9. PCSK9 is an enzyme from the subtilisin-like proprotein convertase family which include proteases that process proteins trafficking through various constitutive secretory pathways. PCSK9 increases blood cholesterol levels by binding to low densitiy lipoprotein (LDL) receptors, targeting them for lysosomal…
Little is known about the interactions of single nucleotide polymorphisms (SNPs) and overweight/obesity on blood pressure levels. The present study was undertaken to detect 10 lipid-related gene SNPs and their interactions with overweight/obesity on blood pressure levels. Genotyping of ATP-binding cassette transporter A1 (ABCA-1) V825I, acyl-CoA:cholesterol acyltransferase-1 (ACAT-1) rs1044925, low density lipoprotein receptor (LDL-R) AvaII hepatic lipase gene (LIPC) −250G | A, endothelial lipase gene (LIPG) 584C | T, methylenetetrahydrofolate reductase (MTHFR) 677C | T, the E3 ubiquitin ligase myosin regulatory light chain-interacting protein (MYLIP) rs3757354, proprotein convertase subtilisin-like kexin type 9 (PCSK9) E670G, peroxisome proliferator-activated receptor delta (PPARD) +294T | C, and Scavenger receptor class B type 1 (SCARB1) rs5888 was performed in 978 normal weight and 751 overweight/obese subjects. The interactions were detected by factorial regression analysis. The genotypes of ACAT
Introduction: Anti-proprotein convertase subtilisin/kexin type 9 (PCSK9) antibodies have been very effective to lower low-density lipoprotein (LDL)-cholesterol. They attracted the attention on PCSK9 enzyme role in multiple pathways and underlined the complex correlations between lipid metabolism and various other liver or extrahepatic diseases, that are insufficiently known. Hepatocyte nuclear factor 1, sterol regulatory element-binding protein (SREBP) 1c and SREBP2 are the main modulators of liver PCSK9 gene and protein expression, processes that can also be influenced by some natural and synthetic compounds (as berberine, or bortezomib and rosuvastatin, respectively), endoplasmic reticulum stress, metabolic status and the diurnal pattern.. Aim: This minireview is an analysis of PCSK9 involvement in liver pathology.. Results and Conclusion: PCSK9 is a key enzyme which increases LDL-receptor degradation. Hepatitis C virus (HCV) enters into hepatocytes in combination with lipoproteins through ...
Policosanol Attenuates Statin-Induced Increases in Serum Proprotein Convertase Subtilisin/Kexin Type 9 When Combined with Atorvastatin - Evid Based Complement Alternat Med. 2014;2014:926087 - Protocol I: 26 patients with atherosclerosis were randomly assigned to receive either atorvastatin 20 mg/d or policosanol 20 mg/d + atorvastatin 20 mg/d for 8 weeks. Protocol II: 15 healthy volunteers were randomly assigned to either policosanol 20 mg/d or a control group for 12 weeks ... Protocol I: atorvastatin 20 mg/d significantly increased serum PCSK9 level by 39.4% (256 ± 84 ng/mL versus 357 ± 101 ng/mL, P = 0.002). However, policosanol 20 mg/d + atorvastatin 20 mg/d increased serum PCSK9 level by only 17.4% without statistical significance (264 ± 60 ng/mL versus 310 ± 86 ng/mL, P = 0.184). Protocol II: there was a trend toward decreasing serum PCSK9 levels in the policosanol group (289 ± 71 ng/mL versus 235 ± 46 ng/mL, P = 0.069) ... Policosanol combined with statin attenuated the ...
PCSK9 inhibitor and high cholesterol. Computer illustration of low-density lipoprotein (LDL, bad cholesterol) molecules (round) bound to LDL receptor (LDLR) proteins, with a molecule of the enzyme proprotein convertase subtilisin/kexin type 9 (PCSK9, blue) bound to a PCSK9 inhibitor antibody (pink). When there are high levels of LDL cholesterol in the blood it builds up on the sides of blood vessels hardening them, a condition named atherosclerosis. This narrows the blood vessels and may block them. LDL receptors recognise and bind to LDL molecules to remove them from the bloodstream. When PCSK9 binds to an LDLR, the receptor is destroyed along with the LDL particle. But if PCSK9 does not bind, the receptor can return to the surface of the cell and remove more cholesterol. Monoclonal antibodies that bind to and inhibit PCSK9 are being used to reduce the amount of cholesterol in the blood by improving the livers ability to recycle LDLRs. - Stock Image C026/3508
Maintaining normal cholesterol levels is critical for warding off heart disease. Proprotein convertase subtilisin kexin type 9 (PCSK9) is a major player in cholesterol regulation - mutations in this gene can lead to familial hypercholesterolemia, a genetic disorder characterized by abnormally high cholesterol levels and cardiovascular disease. Increased PCSK9 activity increases cholesterol levels by binding to low-density lipoprotein receptors (LDLR), which induces receptor degradation and the accumulation of low-density lipoproteins (LDL) in the bloodstream. Thus, high PCSK9 levels normally are associated with high cholesterol levels. However, a 16-week joint study by the University of Florida and Eli Lilly and Company used human volunteers to show that atorvastatin, a widely prescribed cholesterol-reducing drug, increases serum PCSK9 levels while lowering total cholesterol, triglycerides and LDL levels. This indicates that the relationship between PCSK9 and LDL serum levels are disrupted ...
Lipoprotein and PCSK9 bound to receptor. Computer illustration of a low-density lipoprotein (LDL), or bad cholesterol, molecule (round) and a molecule of the enzyme proprotein convertase subtilisin/kexin type 9 (PCSK9, blue) bound to an LDL receptor (LDLR) protein (Y-shaped), with red blood cells (erythrocytes, discs) in a blood vessel (not to scale). When there are high levels of LDL cholesterol in the blood it builds up on the sides of blood vessels hardening them, a condition named atherosclerosis. This narrows the blood vessels and may block them. LDL receptors recognise and bind to LDL molecules to remove them from the bloodstream. When PCSK9 binds to an LDLR, the receptor is destroyed along with the LDL particle. But if PCSK9 does not bind, the receptor can return to the surface of the cell and remove more cholesterol. PCSK9 inhibitor drugs reduce the amount of cholesterol in the blood by improving the livers ability to recycle LDLRs. - Stock Image C026/3517
Hepatitis C virus (HCV) associates with lipoproteins to form "lipoviral particles" (LVPs) that can facilitate viral entry into hepatocytes. Initial attachment occurs via heparan sulphate proteoglycans and low-density lipoprotein receptor (LDLR); CD81 then mediates a post-attachment event. Proprotein convertase subtilisin kexin type 9 (PCSK9) enhances the degradation of the LDLR and modulates liver CD81 levels. We measured LVP and PCSK9 in patients chronically infected with HCV genotype (G)3. PCSK9 concentrations were also measured in HCV-G1 to indirectly examine the role of LDLR in LVP clearance.. ...
Complete information for PCSK9 gene (Protein Coding), Proprotein Convertase Subtilisin/Kexin Type 9, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
Complete information for PCSK1N gene (Protein Coding), Proprotein Convertase Subtilisin/Kexin Type 1 Inhibitor, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
Sepsis is the leading cause of death in critically ill patients. While decreased Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) function improves clinical outcomes in murine and human sepsis, the mechanisms involved have not been fully elucidated. We tested the hypothesis that lipopolysaccharide (LPS), the major Gram-negative bacteria endotoxin, is cleared from the circulation by hepatocyte Low Density Lipoprotein Receptors (LDLR)-receptors downregulated by PCSK9. We directly visualized LPS uptake and found that LPS is rapidly taken up by hepatocytes into the cell periphery. Over the course of 4 hours LPS is transported towards the cell center. We next found that clearance of injected LPS from the blood was reduced substantially in Ldlr knockout (Ldlr-/-) mice compared to wild type controls and, simultaneously, hepatic uptake of LPS was also reduced in Ldlr-/- mice. Specifically examining the role of hepatocytes, we further found that primary hepatocytes isolated from Ldlr-/- mice had ...
However, achieving LDL levels of 70 mg/dL or lower in patients with high initial values is often not possible with statins alone, even with maximum dosages.It needs often combination with other drugs (like ezetimibe). Consequently,the search for new cholesterol-lowering interventions is mandatory.. The number of LDL-R expressed on the surface of hepatocytes is the primary determinant of plasma LDL levels.It binds plasma LDL on the hepatocyte surface, mediating LDL uptake and delivery to the endosomal system, where the LDL particle is released, and the LDL-R is recycled back to the hepatocyte surface to bind LDL particles.. The PCSK9 ("proprotein convertase subtilisin/kexin type 9.")protein appears to control the number of low-density lipoprotein receptors,which determines how quickly cholesterol (in the form of low-density lipoproteins) is removed from the bloodstream. Studies suggest that the PCSK9 protein helps control blood cholesterol levels by breaking down low-density lipoprotein receptors ...
Our recent findings indicate that hepatocyte CD36 is involved in the regulation of the IR (insulin receptor) in the liver and this modulates insulin action on glucose and lipid metabolism, including de-novo lipogenesis (DNL) and hepatic glucose production (HGP). We also identify the influence of hepatic CD36 in transcriptional effects of insulin on Pcsk9 (Proprotein convertase subtilisin/kexin type 9) and Angptl3 (Angiopoietin-like 3), which are essential effectors of triglyceride (TG)/lipoprotein clearance. These findings suggest a link between CD36 signaling, FA flux and insulin action in regulation of liver metabolism and function in lipoprotein clearance. This is highly relevant to our understanding of hepatic insulin sensitivity and diabetic dyslipidemia and etiology of cardiovascular disease ...
Low-frequency coding DNA sequence variants in the proprotein convertase subtilisin/kexin type 9 gene (PCSK9) lower plasma low-density lipoprotein cholesterol (LDL-C), protect against risk of coronary heart disease (CHD), and have prompted the development of a new class of therapeutics. It is uncertain whether the PCSK9 example represents a paradigm or an isolated exception. We used the Exome Array to genotype |200,000 low-frequency and rare coding sequence variants across the genome in 56,538 individuals (42,208 European ancestry [EA] and 14,330 African ancestry [AA]) and tested these variants for association with LDL-C, high-density lipoprotein cholesterol (HDL-C), and triglycerides. Although we did not identify new genes associated with LDL-C, we did identify four low-frequency (frequencies between 0.1% and 2%) variants (ANGPTL8 rs145464906 [c.361C|T; p.Gln121*], PAFAH1B2 rs186808413 [c.482C|T; p.Ser161Leu], COL18A1 rs114139997 [c.331G|A; p.Gly111Arg], and PCSK7 rs142953140 [c.1511G|A; p.Arg504His])
The introduction of singular therapies, such as proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i), to lower high cholesterol levels requires better classification of patients eligible for intensive lipid lowering therapy. According to the European Medicines Administration, PCSK9i are recommended in primary prevention only in familial hypercholesterolemia (FH) patients. Therefore, an FH diagnosis is not simply an academic issue, because it has many clinical implications. The bases of a diagnosis of FH are not entirely clear. The availability of genetic testing, including large genome-wide association analyses and whole genome studies, has shown that some patients with a clinical diagnosis of definite FH have no mutations in the genes associated with the disease. This fact does not exclude the very high cardiovascular risk of these patients, and an early and intensive lipid lowering therapy is recommended in all FH patients. Because an FH diagnosis is a cornerstone for decisions ...
(HealthDay)-Proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies may represent a promising treatment option for acute coronary syndrome (ACS), according to a review published online March 22 in the ...
MONDAY, Oct. 30, 2017 (HealthDay News) -- A combination of clinical factors and payer type increase the likelihood of approval for proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i) treatment, and rates of approval are low overall, according to a study published online Oct. 30 in Circulation.. Gregory P. Hess, M.D., from the University of Pennsylvania in Philadelphia, and colleagues conducted a retrospective cohort study using nationwide pharmacy claims linked to electronic medical records. The data set included more than 220 million patients from all 50 states and all payer types, with 5,140 distinct health plans. In the pharmacy data set, PCSK9i prescriptions were submitted for 51,466 patients. Approval or rejection of PCSK9i prescription claims was the main outcome.. The researchers found that 47 percent of patients who were prescribed a PCSK9i were approved for coverage by the payer. Age ,65 years, history of atherosclerotic cardiovascular disease, prescription by a ...
Values are mean ± SD, n (%), or median (Q1, Q3).. ApoB = apolipoprotein B; ASCVD = atherosclerotic cardiovascular disease; CD4 = cluster of differentiation 4; HDL-C = high-density lipoprotein cholesterol; HIV = human immunodeficiency virus; LDL-C = low-density lipoprotein cholesterol; Lp(a) = lipoprotein(a); NNRTI = non-nucleoside reverse transcriptase inhibitor; NRTI = nucleoside reverse transcriptase inhibitor; PCSK9 = proprotein convertase subtilisin/kexin type 9; Q = quartile; QM = monthly; VLDL-C = very low-density lipoprotein cholesterol.. ...
Alirocumab (SAR236553/REGN727) is a fully human monoclonal antibody that binds PCSK9 (proprotein convertase subtilisin/kexin type 9).. Primary Objective of the study:. To demonstrate the reduction of low-density lipoprotein cholesterol (LDL-C) by alirocumab as add-on therapy to stable maximally tolerated daily statin therapy in comparison with ezetimibe after 24 weeks of treatment in participants with hypercholesterolemia at high cardiovascular (CV) risk.. Secondary Objectives:. ...
Alirocumab (SAR236553/REGN727) is a fully human monoclonal antibody that binds PCSK9 (proprotein convertase subtilisin/kexin type 9).. Primary Objective of the study:. To demonstrate the reduction of low-density lipoprotein cholesterol (LDL-C) by alirocumab as add-on therapy to stable maximally tolerated daily statin therapy in comparison with ezetimibe after 24 weeks of treatment in participants with hypercholesterolemia at high cardiovascular (CV) risk.. Secondary Objectives:. ...
A rare glimpse into the prior authorization requirements implemented by public and private insurance providers across the country has found substantial administrative burden for a new class of medications for patients with high cholesterol that places them at high risk for heart attack or stroke. So-called proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are self-injected medications approved for individuals with a genetic condition called familial hypercholesterolemia (FH) and those with atherosclerotic cardiovascular disease (ASCVD) who have high cholesterol despite receiving traditional statin medications and other treatments. Results of the study are published in Circulation: Cardiovascular Quality and Outcomes.. ...
A rare glimpse into the prior authorization requirements implemented by public and private insurance providers across the country has found substantial administrative burden for a new class of medications for patients with high cholesterol that places them at high risk for heart attack or stroke. So-called proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are self-injected medications approved for individuals with a genetic condition called familial hypercholesterolemia (FH) and those with atherosclerotic cardiovascular disease (ASCVD) who have high cholesterol despite receiving traditional statin medications and other treatments. Results of the study are published in Circulation: Cardiovascular Quality and Outcomes.. ...
Evolocumab (Repatha-Amgen Ltd) and ▼alirocumab (Praluent-Sanofi) are the first in a novel class of lipid-regulating drugs, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, to be licensed in the UK. Both drugs have marketing authorisation for the treatment of primary hypercholesterolaemia (heterozygous familial and non-familial) or mixed dyslipidaemia and are administered by subcutaneous injection.1-3 Here we consider the evidence for evolocumab and alirocumab in the management of primary hypercholesterolaemia and dyslipidaemias. ...
Sanofi and Regeneron hosted an IR Thematic Conference Call for the financial community focusing on alirocumab during the European Society of Cardiology Congress in Barcelona.. Alirocumab (SAR236553/ REGN727) is an investigational monoclonal antibody targeting PCSK9 (proprotein convertase subtilisin/kexin type 9) for the reduction of LDL-cholesterol. Alirocumab is currently being evaluated in a large Phase 3 program in patients with hypercholesterolemia ...
Sanofi and Regeneron hosted an IR Thematic Conference Call for the financial community focusing on alirocumab during the American College of Cardiology Annual Meeting.. Alirocumab (SAR236553/ REGN727) is an investigational monoclonal antibody targeting PCSK9 (proprotein convertase subtilisin/kexin type 9) for the reduction of LDL-cholesterol. Alirocumab is currently being evaluated in a large Phase 3 program in patients with hypercholesterolemia. ...
Title:Pragmatic Analysis of Dyslipidemia Involvement in Coronary Artery Disease: A Narrative Review. VOLUME: 16 ISSUE: 1. Author(s):Romeo-Gabriel Mihăilă*. Affiliation:Faculty of Medicine, "Lucian Blaga" University of Sibiu, Sibiu, Romania; CVASIC Laboratory, Emergency County Clinical Hospital Sibiu, Sibiu. Keywords:Cholesterol, coronary artery disease, dyslipidemia, proprotein convertase subtilisin/kexin type 9, statins, triglycerides.. Abstract:. Background: Dyslipidemia is the main factor involved in the occurrence and progression of coronary artery disease. Objective: The research strategy is aimed at analyzing new data on the pathophysiology of dyslipidemia involvement in coronary artery disease, the modalities of atherogenic risk estimation and therapeutic advances. Methods: Scientific articles published in PubMed from January 2017 to February 2018 were searched using the terms dyslipidemia and ischemic heart disease. Results: PCSK9 contributes to the increase in serum levels of ...
Monoclonal antibody that binds to PCSK9 (proprotein convertase subtilisin/kexin type 9). LDL-C is cleared from the circulation preferentially through t
History: We statement a unique case of renal cholesterol crystal embolism (CCE) induced by carotid artery stenting that was successfully treated with evolocumab, a fully human being monoclonal antibody against proprotein convertase subtilisin kexin type 9 (PCSK9). renal CCE induced by MK-2866 distributor carotid artery stenting that was successfully treated with evolocumab. Case presentation The patient was a 77-year-old man who had been treated for hypertension, hyperlipidemia, and chronic kidney disease with valsartan 40?mg/day and pitavastatin 1?mg/day time. His renal function had been stable, with the serum creatinine around 1.5?mg/dL, estimated glomerular filtration rate (eGFR) 35?mL/min/1.73 m2 as calculated by a modified version of the Changes of Diet in Renal Disease formula of the Japanese Society of Nephrology [10], and no proteinuria. Three months before referral to our department, severe ideal internal carotid artery stenosis was recognized by magnetic resonance angiography which was ...
Matthew Garrett PharmD candidate 2015, Mercer University College of Pharmacy Evolocumab is a human monoclonal antibody that is still in clinical trials. Previous clinical trials have shown that evolocumab along with diet and statins lowers patients LDL levels. Evolocumab is a proprotein convertase subtilisin/kexin type 9 inhibitor, which leads to more low-density lipoprotein (LDL) receptors…
PACE4 antibody (proprotein convertase subtilisin/kexin type 6) for IHC-P. Anti-PACE4 pAb (GTX39485) is tested in Human samples. 100% Ab-Assurance.
Background: Proprotein convertase subtilisin/kexin 9 (PCSK9) is a protein that prevents low-density lipoprotein (LDL) clearance from plasma through degradation of low-density lipoprotein receptors (LDL-R). Mutations that up- or down-regulate PCSK9 have been shown to affect risk of cardiovascular disease independently of plasma LDL level. In light of these discoveries, plasma PCSK9 level may prove useful as a biomarker for cardiovascular risk. Methods: An exhaustive search of the available medical literature was performed using the MEDLINE (Ovid), CINAHL and Web of Science databases. Keywords included PCSK9, evolocumab, alirocumab, myocardial infarction, cardiovascular disease and coronary artery disease (CAD). Inclusion criteria consisted of studies published in English that were performed on a human population, in the absence of statin therapy with endpoints including occurrence of a first cardiovascular event and severity of coronary artery stenosis. Results: Two studies met eligibility criteria for
BACKGROUND AND OBJECTIVE: Heterozygous familial hypercholesterolemia and dyslipidemia are the predominant causes for cardiovascular disease (CVD). Clinical guidelines for lowering CVD risk have advocated that low density lipoprotein-cholesterol (LDL-C) must be reduced. The primary choice of therapy for controlling lipidemia has been statins, which are not completely effective. Proprotein convertase subtilisin/kexin type-9 (PCSK9), which interferes with LDL clearance from circulation, inversely relates to the LDL-C levels. The loss of statin efficacy is likely due to increased circulating PCSK9 and antibody therapy against PCSK9 has been found to be efficacious in lowering LDL-C. In this study, we evaluated the efficacy of PCSK9-mAbs for lowering LDL-C, in statin non-responsive hypercholesterolemia patients. STUDY DESIGN AND METHODS: PubMed, EMBASE, Scholar, Web of Science and Scopus databases were searched to identify randomized controlled trials of PCSK9 antibody-statin combination vs statin, ...
Although cardiovascular disease has been decreasing for decades, it remains the leading cause of death in the United States. Further progress will require both optimal application of proven approaches and the development of new ways to prevent and treat atherosclerosis. Inhibitors of proprotein convertase subtilisin/kexin 9 (PCSK9), which substantially reduce cholesterol levels, are an exciting new approach based on insights from genetics and rational drug development (1). However, the U.S. Food and Drug Administration-approved PCSK9 monoclonal antibodies, alirocumab (2) and evolocumab (3), came to market priced at $14 000 per year-more than 100 times the cost of a generic statin. An ounce of prevention might be worth a pound of cure, but how much is a pound of prevention worth ...
As a recent advertising campaign reminds us, high cholesterol cannot be blamed solely on our unhealthy diets-the genes we inherit play a role as well. Analyzing a large multiethnic population in Texas, Cohen et al. found that individuals with exceptionally low levels of low-density lipoprotein cholesterol (LDL-C), or bad cholesterol, were far more likely than average to carry nonsense mutations in a gene called PCSK9; these mutations were found almost exclusively in African-Americans.. Missense mutations in PCSK9 had previously been identified as the cause of a rare inherited disorder characterized by extremely high cholesterol levels. The PCSK9 product is a serine protease (proprotein convertase subtilisin kexin 9), and an independent study of cultured human liver cells describes its role in cholesterol metabolism. By comparing the properties of cells overexpressing the wild type and a catalytically inactive form of the protease, Maxwell et al. conclude that PCSK9 accelerates the degradation of ...