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https://www.readbyqxmd.com/read/28742217/the-inflammatory-cytokine-interferon-gamma-inhibits-sortilin-1-expression-in-hepatocytes-via-the-jak-stat-pathway
#1
John Pirault, Konstantinos A Polyzos, Marcelo H Petri, Daniel Fj Ketelhuth, Magnus Bäck, Göran K Hansson
Sortilin-1, a receptor of the VPS10p family, has been associated with cardiovascular disease in genome-wide association studies. It is implicated in lipoprotein metabolism, secretion of proprotein convertase subtilisin/kexin type 9 (PCSK9) and secretion of inflammatory cytokines. However, its own regulation remains unclear. Chronic inflammation is a hallmark of atherosclerosis and absence of regulatory T (Treg) cells is associated with reduced protein expression of sortilin-1 in the liver. Therefore, we postulated that mediator(s) of inflammation known to be downregulated by regulatory T cells may modulate sortilin-1 expression...
July 25, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28739196/developing-optimized-treatment-plans-for-patients-with-dyslipidemia-in-the-era-of-pcsk9-inhibitor-therapeutics
#2
James A Underberg, Michael J Blaha, Elizabeth J Jackson Msn, Peter H Jones
This educational content was derived from live, satellite symposium at the American College of Physicians (ACP) Internal Medicine Meeting 2017 in San Diego, California (online at http://courses.elseviercme.com/acp/702e). This activity will focus on optimized treatment plans for patients with dyslipidemia in the era of PCSK9 inhibitor therapeutics. LDL-C has been identified as an important therapeutic target to prevent the progression of atherosclerotic disease, however only 1 out of every 3 adults with high LDL-C has the condition under control...
July 21, 2017: American Journal of Medicine
https://www.readbyqxmd.com/read/28738813/efficacy-and-safety-of-proprotein-convertase-subtilisin-kexin-type-9-pcsk9-inhibitors-alirocumab-and-evolocumab-a-post-commercialization-study
#3
Joshua Choi, Amir M Khan, Michael Jarmin, Naila Goldenberg, Charles J Glueck, Ping Wang
BACKGROUND: Efficacy-safety of proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors, alirocumab (ALI) and evolocumab (EVO), have previously been evaluated through controlled clinical trials with selective patient groups. Post-commercially, in 69 patients with heterozygous familial hypercholesterolemia (HeFH) and/or cardiovascular disease (CVD) with suboptimal LDL cholesterol (LDLC) lowering on maximal tolerated LDLC therapy, we assessed efficacy and safety of ALI and EVO. METHODS: Post-commercially, we started 29 patients on ALI 75 mg, 18 on ALI 150 mg, and 22 on EVO 140 mg every 2 weeks added to a maximally tolerated LDLC-lowering regimen...
July 24, 2017: Lipids in Health and Disease
https://www.readbyqxmd.com/read/28738115/inconsistent-guideline-recommendations-for-cardiovascular-prevention-and-the-debate-about-zeroing-in-on-and-zeroing-ldl-c-levels-with-pcsk9-inhibitors
#4
John P A Ioannidis
No abstract text is available yet for this article.
July 24, 2017: JAMA: the Journal of the American Medical Association
https://www.readbyqxmd.com/read/28736830/pcsk9-in-context-a-contemporary-review-of-an-important-biological-target-for-the-prevention-and-treatment-of-atherosclerotic-cardiovascular-disease
#5
REVIEW
Michael M Page, Gerald F Watts
Proprotein convertase subtilisin/kexin type 9 (PCSK9) and the identification of its critical role in lipoprotein metabolism has rapidly led to the development of PCSK9 inhibition with monoclonal antibodies (mAbs). PCSK9 mAbs are already in limited clinical use and are the subject of major cardiovascular outcomes trials, which if universally positive could see much wider clinical application of these agents. Patients with familial hypercholesterolaemia are the most obvious candidates for these drugs, but other patients with elevated cardiovascular risk, statin intolerance or hyperlipoproteinaemia(a) may also benefit...
July 24, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28735360/navigating-the-future-of-cardiovascular-drug-development-leveraging-novel-approaches-to-drive-innovation-and-drug-discovery-summary-of-findings-from-the-novel-cardiovascular-therapeutics-conference
#6
REVIEW
Thomas J Povsic, Rob Scott, Kenneth W Mahaffey, Robert Blaustein, Jay M Edelberg, Martin P Lefkowitz, Scott D Solomon, Jonathan C Fox, Kevin E Healy, Aarif Y Khakoo, Douglas W Losordo, Fady I Malik, Brett P Monia, Rusty L Montgomery, Jeffrey Riesmeyer, Gregory G Schwartz, Steven L Zelenkofske, Joseph C Wu, Scott M Wasserman, Matthew T Roe
PURPOSE: The need for novel approaches to cardiovascular drug development served as the impetus to convene an open meeting of experts from the pharmaceutical industry and academia to assess the challenges and develop solutions for drug discovery in cardiovascular disease. METHODS: The Novel Cardiovascular Therapeutics Summit first reviewed recent examples of ongoing or recently completed programs translating basic science observations to targeted drug development, highlighting successes (protein convertase sutilisin/kexin type 9 [PCSK9] and neprilysin inhibition) and targets still under evaluation (cholesteryl ester transfer protein [CETP] inhibition), with the hope of gleaning key lessons to successful drug development in the current era...
July 22, 2017: Cardiovascular Drugs and Therapy
https://www.readbyqxmd.com/read/28734274/genetic-analysis-of-iranian-patients-with-familial-hypercholesterolemia
#7
Mahdis Ekrami, Maryam Torabi, Soudeh Ghafouri-Fard, Javad Mowla, Bahram Mohammad Soltani, Feyzollah Hashemi-Gorji, Zahra Mohebbi, Mohammad Miryounesi
Background: Familial hypercholesterolemia (FH) is a frequent autosomal dominant disorder of lipoprotein metabolism. This disorder is generally caused by mutations in low-density lipoprotein receptor (LDLR), apolipoprotein B 100 (APOB), and proprotein convertase subtilisin/kexin type 9 (PCSK9) genes. In the present study, we aimed at identifying the common LDLR and APOB gene mutations in an Iranian population. Methods: Eighty unrelated Iranian patients with FH entered the study, based on Simon Broome diagnostic criteria...
July 23, 2017: Iranian Biomedical Journal
https://www.readbyqxmd.com/read/28728483/pcsk9-inhibition-in-statin-intolerant-hefh-patients-what-s-new
#8
Manuela Casula, Angela Pirillo, Giuseppe Danilo Norata, Alberico Luigi Catapano
No abstract text is available yet for this article.
January 1, 2017: European Journal of Preventive Cardiology
https://www.readbyqxmd.com/read/28727814/low-pcsk9-levels-are-correlated-with-mortality-in-patients-with-end-stage-liver-disease
#9
Valentin Schlegel, Theresa Treuner-Kaueroff, Daniel Seehofer, Thomas Berg, Susen Becker, Uta Ceglarek, Joachim Thiery, Thorsten Kaiser
INTRODUCTION: Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a key role in the cholesterol metabolism and is synthesized by the liver. It interacts with the LDL-receptor to promote its degradation. The model of end-stage liver disease (MELD) score is a well-established tool to estimate the risk of mortality in patients with end-stage chronic liver disease. The study aims to assess the associations between PCSK9, hypocholesterinemia, liver synthesis, cholestasis, MELD score and mortality in patients with end-stage liver disease...
2017: PloS One
https://www.readbyqxmd.com/read/28727332/-inhibitors-of-pcsk9
#10
Iveta Petrova-Slater, Andrea Denegri, Elena Pasotti, Maria Grazia Rossi, David Spirk, Walter F Riesen, Tiziano Moccetti, Marco Moccetti
Observational data show a consistent association between elevated low density lipoproteins (LDL-C) and cardiovascular disease (CVD). Reduction of LDL-C reduces the risk of CVD as has been shown by many trials. Statins are currently the most effective drugs for lowering LDL-C, but can present side effects which might limit the prescribed dosage and prevent patients from reaching the recommended LDL levels. Although treated with statins important residual cardiovascular event risk remains in patients in primary and secondary prevention for CVD...
April 12, 2017: Revue Médicale Suisse
https://www.readbyqxmd.com/read/28726431/-what-has-the-glagov-clinical-study-shown
#11
Ján Murín
If we want to favorably influence the cardiovascular atherosclerotic disease, it is necessary to significantly lower LDL-C blood levels. PCSK9 inhibitors can significantly reduce LDL-cholesterol levels, being administered together with statins. However we focus on establishing whether this plays a role in influencing coronary atherosclerosis. The GLAGOV study is a multicentric, double-blinded and placebo-controlled study which during a 76-week period followed an impact of the treatment with evolocumab (PCSK9i) together with statin on the status of coronary atherosclerosis in patients with ischemic heart disease, and in comparison with the statin treatment...
2017: Vnitr̆ní Lékar̆ství
https://www.readbyqxmd.com/read/28726204/association-of-level-of-proprotein-convertase-subtilisin-kexin-type-9-with-intima-media-thickness-in-patients-with-familial-hypercholesterolemia
#12
K S Benimetskaya, Yu I Ragino, E V Shakhtshneider, K V Makarenkova, Yu V Shchepina, E M Stakhneva, M I Voevoda
We studied association of PCSK9 protein with the carotid artery intima-media thickness in patients with familial hypercholesterolemia (N=53; age 49.9±6.9 years) treated with statins. Blood level of PCSK9 protein was measured by ELISA; ultrasonography of the carotid arteries with measurement of the thickness of the intima-media complex of the common carotid arteries in the distal segment for 10 mm from the bifurcation on the far wall of the vessel was performed in on-line mode. The mean values were calculated for both sides, the maximum mean value was included in the analysis...
July 18, 2017: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28722331/hepatitis-c-virus-and-proprotein-convertase-subtilisin-kexin-type-9-a-detrimental-interaction-to-increase-viral-infectivity-and-disrupt-lipid-metabolism
#13
REVIEW
Matteo Pirro, Vanessa Bianconi, Daniela Francisci, Elisabetta Schiaroli, Francesco Bagaglia, Amirhossein Sahebkar, Franco Baldelli
From viral binding to the hepatocyte surface to extracellular virion release, the replication cycle of the hepatitis C virus (HCV) intersects at various levels with lipid metabolism; this leads to a derangement of the lipid profile and to increased viral infectivity. Accumulating evidence supports the crucial regulatory role of proprotein convertase subtilisin/kexin type 9 (PCSK9) in lipoprotein metabolism. Notably, a complex interaction between HCV and PCSK9 has been documented. Indeed, either increased or reduced circulating PCSK9 levels have been observed in HCV patients; this discrepancy might be related to several confounders, including HCV genotype, human immunodeficiency virus (HIV) coinfection and the ambiguous HCV-mediated influence on PCSK9 transcription factors...
July 18, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28721209/recent-advances-in-preventing-stroke-recurrence
#14
REVIEW
J David Spence
Recent advances in secondary stroke prevention include new evidence in hypertension, nutrition, anticoagulation, antiplatelet therapy, intracranial stenosis, percutaneous closure of patent foramen ovale, and lipid-lowering therapy. Individualized therapy for hypertension based on phenotyping with plasma renin and aldosterone markedly improves blood pressure control in patients with resistant hypertension. A Mediterranean diet can reduce the risk of stroke by nearly half. The diagnosis and treatment of metabolic vitamin B12 deficiency, and B vitamins to lower homocysteine, can reduce the risk of stroke by approximately 30%...
2017: F1000Research
https://www.readbyqxmd.com/read/28721159/pcsk9-inhibitors-from-discovery-of-a-single-mutation-to-a-groundbreaking-therapy-of-lipid-disorders-in-one-decade
#15
Krzysztof Jaworski, Piotr Jankowski, Dariusz A Kosior
Hypercholesterolemia is one of the main risk factors for coronary heart disease and significantly contributes to the high mortality associated with cardiovascular diseases. Statin therapy represents the gold standard in the reduction of low-density lipoprotein cholesterol concentration. Nevertheless, many patients still cannot achieve the recommended target levels, due to either inadequate effectiveness or intolerance of these drugs. Monoclonal antibodies that inhibit proprotein convertase subtilisin/kexin type 9 (PCSK9) have emerged as a promising option in lipid-lowering treatment...
June 2017: Archives of Medical Science: AMS
https://www.readbyqxmd.com/read/28717862/practical-considerations-for-the-use-of-subcutaneous-treatment-in-the-management-of-dyslipidaemia
#16
REVIEW
Franck Boccara, Ricardo Dent, Luis Ruilope, Paul Valensi
Suboptimal drug adherence represents a major challenge to effective primary and secondary prevention of cardiovascular disease. While adherence is influenced by multiple considerations, polypharmacy and dosing frequency appear to be rate-limiting factors in patient satisfaction and subsequent adherence. The cardiovascular and metabolic therapeutic areas have recently benefited from a number of advances in drug therapy, in particular protease proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors and incretin-based therapies, respectively...
July 17, 2017: Advances in Therapy
https://www.readbyqxmd.com/read/28711549/a-case-of-hypocholesterolemia-and-steatosis-in-a-carrier-of-a-pcsk9-loss-of-function-mutation-and-polymorphisms-predisposing-to-nonalcoholic-fatty-liver-disease
#17
Mathilde Di Filippo, Benoit Vokaer, Nabil G Seidah
We report a new case of hypobetalipoproteinemia in a 44-year-old man of Peruvian origin exhibiting a heterozygous PCSK9 missense mutation (c.946 G>T, p. Gly316Cys). In vitro functional studies demonstrated that this mutation leads to a loss of function of PCSK9 on low-density lipoprotein receptor degradation. This patient exhibited liver steatosis; he was neither diabetic, nor obese or alcoholic, but is a carrier of 2 polymorphisms, p.Ile148Met (rs738409) and p.Glu167Lys (rs58542926) on PNPLA3 and TM6SF2 gene, respectively, previously shown to be associated with nonalcoholic steatosis and fibrosis evolution...
June 13, 2017: Journal of Clinical Lipidology
https://www.readbyqxmd.com/read/28709786/-pcsk-9-inhibitors-effects-on-ldl-c-and-future-implications-what-you-should-know
#18
P Corral, A J Ruiz
The discovery of proprotein convertase subtilisin/kexin type 9 (PCSK9) in 2003 in families with familial hypercholesterolemia (HF) later generated the development of pharmacological strategies in order to inhibit this protein. Twelve years after this discovery, the first two biological compounds (monoclonal antibodies) were approved, which have been shown to substantially decrease LDL-C and other lipid subfractions. The objective of the present article is to review the history of the discovery of PCSK9, its physiology and pathophysiology and subsequent pharmacological development...
July 11, 2017: Hipertensión y Riesgo Vascular
https://www.readbyqxmd.com/read/28707678/cardiovascular-endocrinology-is-angptl3-the-next-pcsk9
#19
Kiran Musunuru, Sekar Kathiresan
No abstract text is available yet for this article.
July 14, 2017: Nature Reviews. Endocrinology
https://www.readbyqxmd.com/read/28705542/effect-of-coronary-artery-disease-risk-snps-on-serum-cytokine-levels-and-cytokine-imbalance-in-premature-coronary-artery-disease
#20
Wafa M Ansari, Steve E Humphries, Abdul K Naveed, Omer J Khan, Dilshad A Khan, Ejaz Hassan Khattak
BACKGROUND: Premature Coronary Artery Disease (PCAD) occurs almost a decade earlier in the South Asian population as compared to the West. Inclusion of genetic information can prove to be a robust measure to improve early risk prediction of PCAD. Aim was to estimate the genotypic distribution and risk allele frequencies of 13 Coronary Artery Disease (CAD) risk Single Nucleotide Polymorphisms in loci identified by the CARDIoGRAMplusC4D consortium namely MIA3 rs17465637; 9p21 rs10757274; CXCL12 rs1746048; APOA5 rs662799; APOB rs1042031; LPA rs3798220; LPA 10455872; MRAS rs9818870; LPL rs328; SORT1 rs646776; PCSK9 rs11591147; APOE rs429358; APOE rs7412 in Pakistani PCAD patients and controls...
July 10, 2017: Cytokine
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