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https://www.readbyqxmd.com/read/28110294/proprotein-convertase-subtilisin-kexin-type-9-pcsk9-inhibitors-comparing-and-contrasting-guidance-across-the-atlantic
#1
EDITORIAL
Marc S Sabatine
No abstract text is available yet for this article.
January 21, 2017: European Heart Journal
https://www.readbyqxmd.com/read/28109622/genetics-for-the-identification-of-lipid-targets-beyond-pcsk9
#2
REVIEW
Linda R Wang, Robert A Hegele
From studies of rare families to genome-wide associations in populations, understanding of human genetics has accelerated the search for new drug targets for the prevention of atherosclerotic cardiovascular disease. DNA sequencing and genome-wide analyses of DNA markers have illuminated rare as well as common variants in genes that regulate lipids and ultimately atherosclerosis risk. A recent innovative approach called Mendelian randomization can endorse specific genes and variants as causative not just for lipid disturbances, but also for clinical cardiovascular end points...
November 11, 2016: Canadian Journal of Cardiology
https://www.readbyqxmd.com/read/28108631/the-complexity-of-lipoprotein-a-lowering-by-pcsk9-monoclonal-antibodies
#3
REVIEW
Gilles Lambert, Aurélie Thedrez, Mikaël Croyal, Stéphane Ramin-Mangata, David Couret, Nicolas Diotel, Estelle Nobécourt-Dupuy, Michel Krempf, Jean Christophe LeBail, Bruno Poirier, Jorg Blankenstein, Elise F Villard, Etienne Guillot
Since 2012, clinical trials dedicated to proprotein convertase subtilisin kexin type 9 (PCSK9) inhibition with monoclonal antibodies (mAbs) have unambiguously demonstrated robust reductions not only in low-density lipoprotein (LDL) cholesterol (LDL-C) but also in lipoprotein (a) [Lp(a)] levels. The scientific literature published prior to those studies did not provide any evidence for a link between PCSK9 and Lp(a) metabolism. More recent investigations, either in vitro or in vivo, have attempted to unravel the mechanism(s) by which PCSK9 mAbs reduce circulating Lp(a) levels, with some showing a specific implication of the LDL receptor (LDLR) in Lp(a) clearance whereas others found no significant role for the LDLR in that process...
February 1, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28104607/pcsk9-inhibitors-for-hypercholesterolaemia
#4
Patricia McGettigan, Robin E Ferner
No abstract text is available yet for this article.
January 19, 2017: BMJ: British Medical Journal
https://www.readbyqxmd.com/read/28104544/molecular-genetics-of-familial-hypercholesterolemia-in-israel-revisited
#5
Ronen Durst, Uche Ken Ibe, Shoshi Shpitzen, Daniel Schurr, Osnat Eliav, Marta Futema, Ros Whittall, Auryan Szalat, Vardiella Meiner, Hilla Knobler, Dov Gavish, Yaakov Henkin, Avishay Ellis, Ardon Rubinstein, Dror Harats, Rafael Bitzur, Bruno Hershkovitz, Steve E Humphries, Eran Leitersdorf
BACKGROUND AND AIMS: Familial hypercholesterolemia (FH) is an autosomal dominant disease caused by mutations in the genes for LDL receptor (LDLR), apolipoprotein B (APOB) and proprotein convertase subtilisin/kexin type9 (PCSK9). The purpose of the current investigation was to define the current spectrum of mutations causing FH in Israel. METHODS: New families were collected through the MEDPED (Make Early Diagnosis Prevent Early Death) FH program. Molecular analysis of the LDLR, PCSK9 and APOB genes was done using High Resolution Melt and direct sequencing in 67 index cases...
December 18, 2016: Atherosclerosis
https://www.readbyqxmd.com/read/28100270/pro-inflammation-nf-%C3%AE%C2%BAb-signaling-triggers-a-positive-feedback-via-enhancing-cholesterol-accumulation-in-liver-cancer-cells
#6
Mingyan He, Wenhui Zhang, Yinying Dong, Lishun Wang, Tingting Fang, Wenqing Tang, Bei Lv, Guanglang Chen, Biwei Yang, Peixin Huang, Jinglin Xia
BACKGROUND: Hepatocellular carcinoma (HCC) develops in a complex microenvironment characterized by chronic inflammation. In recent years, cholesterol metabolic abnormalities have been implicated the importance in cancer cell physiology. This study was designed to investigate the relationship between inflammation and cholesterol accumulation in HCC cells. METHODS: Human HCC cells HepG2 and Huh7 were cultured and stimulated with lipopolysaccharide (LPS) for 24 h...
January 18, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28096572/current-and-emerging-treatments-for-hypercholesterolemia-a-focus-on-statins-and-proprotein-convertase-subtilisin-kexin-type-9-inhibitors-for-perioperative-clinicians
#7
REVIEW
Terrence L Trentman, Steven G Avey, Harish Ramakrishna
Statins are a mainstay of hyperlipidemia treatment. These drugs inhibit the enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase and have beneficial effects on atherosclerosis including plaque stabilization, reduction of platelet activation, and reduction of plaque proliferation and inflammation. Statins also have a benefit beyond atherosclerotic plaque, including anticoagulation, vasodilatation, antioxidant effects, and reduction of mediators of inflammation. In the perioperative period, statins appear to contribute to improved outcomes via these mechanisms...
October 2016: Journal of Anaesthesiology, Clinical Pharmacology
https://www.readbyqxmd.com/read/28093849/obesity-and-type-2-diabetes-are-associated-with-elevated-pcsk9-levels-in-young-women
#8
Amy E Levenson, Amy S Shah, Philip R Khoury, Thomas R Kimball, Elaine M Urbina, Sarah D de Ferranti, David M Maahs, Lawrence M Dolan, R Paul Wadwa, Sudha B Biddinger
BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a key regulator of low-density lipoprotein cholesterol and cardiovascular disease risk, and is an emerging therapeutic target. OBJECTIVE: We compared serum PCSK9 levels in young adults, with and without type 2 diabetes. SUBJECTS AND METHODS: Cross-sectional analysis was conducted in a cohort, aged 15 to 26 years, in Cincinnati, OH, from 2005 to 2010. Serum PCSK9 levels were measured in 94 youth with type 2 diabetes, 93 obese control subjects, and 99 lean control subjects...
January 17, 2017: Pediatric Diabetes
https://www.readbyqxmd.com/read/28089936/biodegradable-lipid-nanoparticles-induce-a-prolonged-rna-interference-mediated-protein-knockdown-and-show-rapid-hepatic-clearance-in-mice-and-nonhuman-primates
#9
Yuta Suzuki, Kenji Hyodo, Takuya Suzuki, Yohei Tanaka, Hiroshi Kikuchi, Hiroshi Ishihara
Lipid nanoparticles based on ionizable lipids have been clinically validated as a means of delivery for RNA interference (RNAi) therapeutics. The ideal properties of RNAi carriers are efficient delivery of oligonucleotides into target cells and rapid elimination after the function is performed. Here, we report that degradable lipid nanoparticles are effective carriers of small interfering RNA (siRNA) and have a high therapeutic index. The newly developed degradable lipid nanoparticles carrying siRNA showed potent gene-silencing activity in mouse hepatocytes (ED50≈0...
January 9, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28087751/odyssey-escape-is-pcsk9-inhibition-the-trojan-horse-for-the-use-of-lipoprotein-apheresis-in-familial-hypercholesterolaemia
#10
EDITORIAL
Gerald F Watts, Claudia Stefanutti
No abstract text is available yet for this article.
December 21, 2016: European Heart Journal
https://www.readbyqxmd.com/read/28087743/updates-on-prevention-obesity-ezetimibe-pcsk9-and-hiv-infection
#11
EDITORIAL
Thomas F Lüscher
No abstract text is available yet for this article.
December 21, 2016: European Heart Journal
https://www.readbyqxmd.com/read/28081164/economic-evaluation-of-pcsk9-inhibitors-in-reducing-cardiovascular-risk-from-health-system-and-private-payer-perspectives
#12
Alejandro Arrieta, Timothy F Page, Emir Veledar, Khurram Nasir
The introduction of Proprotein covertase subtilisin/kexin type 9 (PCSK9) inhibitors has been heralded as a major advancement in reducing low-density lipoprotein cholesterol levels by nearly 50%. However, concerns have been raised on the added value to the health care system in terms of their costs and benefits. We assess the cost-effectiveness of PCSK9 inhibitors based on a decision-analytic model with existing clinical evidence. The model compares a lipid-lowering therapy based on statin plus PCSK9 inhibitor treatment with statin treatment only (standard therapy)...
2017: PloS One
https://www.readbyqxmd.com/read/28073851/increased-risk-of-adverse-neurocognitive-outcomes-with-proprotein-convertase-subtilisin-kexin-type-9-inhibitors
#13
Abdur Rahman Khan, Chirag Bavishi, Haris Riaz, Talha A Farid, Sobia Khan, Michel Atlas, Glenn Hirsch, Sohail Ikram, Roberto Bolli
BACKGROUND: There is encouraging evidence of the efficacy of proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors; however, their long-term safety remains unclear. We performed a meta-analysis of studies to evaluate the long-term safety of PCSK9 inhibitors. METHODS AND RESULTS: Our search strategy yielded 11 studies (9 smaller early-phase and 2 larger outcome trials). The outcomes assessed were cumulative serious adverse events, musculoskeletal adverse events, neurocognitive adverse events, and stroke...
January 2017: Circulation. Cardiovascular Quality and Outcomes
https://www.readbyqxmd.com/read/28064066/plasma-pcsk9-measurement-by-liquid-chromatography-tandem-mass-spectrometry-and-comparison-with-conventional-elisa
#14
Mikaël Croyal, Fanta Fall, Michel Krempf, Aurélie Thédrez, Khadija Ouguerram, Véronique Ferchaud-Roucher, Audrey Aguesse, Stéphanie Billon-Crossouard, Pedro Mata, Rodrigo Alonso, Gilles Lambert, Estelle Nobécourt
The combination of liquid chromatography-tandem mass spectrometry (LC-MS/MS) and trypsin proteolysis is an effective tool for accurate quantitation of multiple proteins in a single run. However, expensive samples pre-treatment as immunoenrichment are often required to analyze low abundant proteins. Plasma proprotein convertase subtilisin/kexin type 9 (PCSK9), a circulating regulator of low-density lipoprotein metabolism, was studied as an example of a low abundant plasma protein. We investigated post-proteolysis solid-phase extraction (SPE) as an alternative strategy to improve its detection...
December 31, 2016: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/28063230/pcsk9-at-the-crossroad-of-cholesterol-metabolism-and-immune-function-during-infections
#15
REVIEW
Francesco Paciullo, Francesca Fallarino, Vanessa Bianconi, Massimo R Mannarino, Amirhossein Sahebkar, Matteo Pirro
Sepsis, a complex and dynamic syndrome resulting from microbial invasion and immune system dysregulation, is associated with an increased mortality, reaching up to 35% worldwide. Cholesterol metabolism is often disturbed during sepsis, with low plasma cholesterol levels being associated with poor prognosis. Proprotein convertase subtilisin/kexin type 9 (PCSK9) promotes degradation of the low-density lipoprotein receptor (LDLR), thus regulating intracellular and plasma cholesterol levels. PCSK9 is often upregulated during sepsis and might have a detrimental effect on immune host response and survival...
January 7, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28060539/bococizumab-for-the-treatment-of-hypercholesterolaemia
#16
Nicola Ferri, Alberto Corsini, Cesare R Sirtori, Massimiliano Ruscica
Low-density lipoprotein cholesterol (LDL-C) remains a well-established risk factor for cardiovascular disease (CVD). LDL-C levels are considered primary targets of therapy. A new series of systemic biomolecules, the monoclonal antibodies (mAbs) of proprotein convertase subtilisin/kexin type 9 (PCSK9), have a higher activity in reducing LDL-C. Areas covered: The authors critically review the current evidence on the efficacy and safety of bococizumab, a humanized mAb against PCSK9, which was surprisingly discontinued in November 2016...
February 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28038950/pcsk9-inhibitors-in-the-current-management-of-atherosclerosis
#17
Thomas F Whayne
The history of proprotein convertase subtilisin/kexin type 9 (PCSK9) in medical science is fascinating and the evolution of knowledge of its function has resulted in new medications of major importance for the cardiovascular (CV) patient. PCSK9 functions as a negative control or feedback for the cell surface receptors for low-density lipoprotein including its component of cholesterol (LDL-C). The initial and key findings were that different abnormalities of PCSK9 can result in an increase or a decrease of LDL-C because of more or less suppression of cell surface receptors...
January 2017: Archivos de Cardiología de México
https://www.readbyqxmd.com/read/28036293/a-retrospective-study-of-nens-and-mir-224-promotes-apoptosis-of-bon-1-cells-by-targeting-pcsk9-inhibition
#18
Jian'an Bai, He Na, Xiumei Hua, Yaling Wei, Tian Ye, Yiqiang Zhang, Guo Jian, Weiwen Zeng, Lijun Yan, Qiyun Tang
Neuroendocrine neoplasms (NENs) represent relatively rare tumors. The lack of diagnostic, therapeutic method and prognostic factors makes them a challenge to us. We retrospectively reviewed the data of 205 NENs patients among which 157 cases were followed-up. Proprotein convertase subtilisin/kexin 9 (PCSK9), a regulator of low density lipoprotein cholesterol (LDL-C), was confirmed as a target gene of microRNA-224. We found an increased incidence of NENs from 2012 to 2015. Women were usually diagnosed at earlier stages than men (P < 0...
December 28, 2016: Oncotarget
https://www.readbyqxmd.com/read/28028691/sirolimus-therapy-is-associated-with-elevation-in-circulating-pcsk9-levels-in-cardiac-transplant-patients
#19
Vinaya Simha, Sisi Qin, Pankaj Shah, Byron H Smith, Walter K Kremers, Sudhir Kushwaha, Liewei Wang, Naveen L Pereira
Sirolimus used in transplantation is often associated with hypercholesterolemia. We measured serum lipid and PCSK9 levels in 51 heart transplant recipients who had their immunosuppressive therapy switched from calcineurin inhibitors to sirolimus. The switch resulted in a 23% increase in LDL cholesterol, and 46% increase in triglycerides and PCSK9 levels increased from 316 ± 105 ng/mL to 343 ± 107 ng/mL (p = 0.04), however the change in PCSK9 levels did not correlate with an increase in lipid levels (p = 0...
December 27, 2016: Journal of Cardiovascular Translational Research
https://www.readbyqxmd.com/read/28025677/pcsk9-inhibition-the-dawn-of-a-new-age-in-cholesterol-lowering
#20
REVIEW
David Preiss, Marion Mafham
Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a circulating enzyme of hepatic origin that plays a key role in LDL receptor turnover. Genetic studies have confirmed that individuals with gain-of-function PCSK9 mutations have increased PCSK9 activity, elevated LDL-cholesterol levels and a severe form of familial hypercholesterolaemia. Those with variants leading to reduced PCSK9 have lower LDL-cholesterol levels and a reduced risk of coronary heart disease, and this has led to the development of various strategies aimed at reducing circulating PCSK9...
December 26, 2016: Diabetologia
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