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https://www.readbyqxmd.com/read/29766560/further-options-for-treating-lipids-in-people-with-diabetes-targeting-ldl-cholesterol-and-beyond
#1
REVIEW
A S Wierzbicki
Diabetes is associated with increased cardiovascular disease (CVD) risk. Previous studies with statins have established that a 1 mmol/l reduction in LDL-cholesterol reduces CVD events by 21% over 5 years in people with diabetes. More recently, trials in people with acute coronary syndromes showed that ezetimibe reduced CVD events by 6% at 5 years and achieved a LDL-cholesterol of 1.6 mmol/l with better results in people with Type 2 diabetes. Several novel lipid-lowering therapies have recently been developed...
May 15, 2018: Diabetic Medicine: a Journal of the British Diabetic Association
https://www.readbyqxmd.com/read/29754911/pcsk-9-entering-a-new-era-of-cardiovascular-risk-prediction
#2
EDITORIAL
Thomas H Schindler, Thorsten M Leucker
No abstract text is available yet for this article.
July 15, 2018: International Journal of Cardiology
https://www.readbyqxmd.com/read/29567472/soat1-deficiency-attenuates-atherosclerosis-by-regulating-inflammation-and-cholesterol-transportation-via-ho-1-pathway
#3
Nan Wu, Rong-Qing Li, Li Li
Sterol O-acyltransferase 1 (SOAT1) is a key enzyme for cholesteryl ester biosynthesis. The objective of the present study is to investigate the role and underlying molecular mechanisms of SOAT1 in atherosclerosis. Our results indicated that SOAT1 was highly expressed in endothelial cells of atherosclerotic lesions in human patients with atherosclerosis and in apolipoprotein E deficient (ApoE-/- ) mice fed with high fat diet (HFD). We established a model of atherosclerosis using ApoE and SOAT1 gene double knockout (ApoE-/- SOAT1-/- ) mice...
March 19, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29495284/discovery-of-flavonoids-from-scutellaria-baicalensis-with-inhibitory-activity-against-pcsk-9-expression-isolation-synthesis-and-their-biological-evaluation
#4
Piseth Nhoek, Hee-Sung Chae, Jagadeesh Nagarajappa Masagalli, Karabasappa Mailar, Pisey Pel, Young-Mi Kim, Won Jun Choi, Young-Won Chin
Nine flavonoids were isolated and identified from a chloroform-soluble fraction of the roots of Scutellaria baicalensis through a bioactivity-guided fractionation using a proprotein convertase subtilisin/kexin type 9 (PCSK9) monitoring assay in HepG2 cells. All structures were established by interpreting the corresponding spectroscopic data and comparing measured values from those in the literature. All compounds were assessed for their ability to inhibit PCSK9 mRNA expression; compounds 1 (3,7,2'-trihydroxy-5-methoxy-flavanone) and 4 (skullcapflavone II) were found to suppress PCSK9 mRNA via SREBP-1...
February 24, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29438441/development-of-vaccine-for-dyslipidemia-targeted-to-a-proprotein-convertase-subtilisin-kexin-type-9-pcsk9-epitope-in-mice
#5
Ryo Kawakami, Yoichi Nozato, Hironori Nakagami, Yuka Ikeda, Munehisa Shimamura, Shota Yoshida, Jiao Sun, Tomohiro Kawano, Yoichi Takami, Takahisa Noma, Hiromi Rakugi, Tetsuo Minamino, Ryuichi Morishita
Proprotein convertase subtilisin/kexin type 9 (PCSK9) regulates expression of low-density lipoprotein (LDL) receptors via receptor internalization and subsequent lysosomal degradation. Thus, an anti-PCSK9 antibody is well known as an anti-hyperlipidemia drug. Here, we aimed to develop vaccine for a long-term treatment of dyslipidemia targeted to PCSK9. In This study, we designed a peptide vaccine for mouse PCSK-9, which consisted of short peptides conjugated to keyhole limpet hemocyanin (KLH) as a carrier protein...
2018: PloS One
https://www.readbyqxmd.com/read/29422010/berberine-encapsulated-plga-peg-nanoparticles-modulates-pcsk-9-in-hepg2-cells
#6
Chinedu Ochin, Mahdi Garelnabi
BACKGROUND: The developments of new parenteral approaches to target PCSK-9 for the treatment LDL-Cholesterol has yielded impressive results; and have shown significant decreases in the risk of mortality associated with hypercholesterolemia. However improved and convenient alternate approaches that exploit the beneficial drug target properties of PCSK-9 also need to be explored and developed. One such approach is the oral administration of Berberine using nanotechnology. METHODS: Nanoprecipitation encapsulation and physiochemical characterization of Berberine Chloride in PLGA-PEG-PLGA block copolymer has been developed and characterized in Hep-G2 cells using Berberine Chloride encapsulated nanoparticle (BC-NP)...
February 1, 2018: Cardiovascular & Hematological Disorders Drug Targets
https://www.readbyqxmd.com/read/29174038/lycopene-amends-lps-induced-oxidative-stress-and-hypertriglyceridemia-via-modulating-pcsk-9-expression-and-apo-ciii-mediated-lipoprotein-lipase-activity
#7
Sahir Sultan Alvi, Irfan A Ansari, Mohammad Kaleem Ahmad, Johar Iqbal, M Salman Khan
This study was undertaken to uncover the regulatory role of lycopene in targeting lipopolysaccharide (LPS) induced oxidative stress and inflammatory cascades and subsequent regulation of proprotein convertase subtilisin/kexin type-9 (PCSK-9) expression via sterol regulatory element binding protein-2 (SREBP-2) and hepatocyte nuclear factor-1α (HNF-1α). Further, protein-protein interaction (PPI) studies for Lycopene-Apo-CIII complex against lipoprotein lipase (LPL) were also performed to assess its regulatory role behind the enhanced circulatory TG/TRLs clearance...
December 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29151496/cost-effectiveness-analysis-of-cardiovascular-disease-treatment-in-japan
#8
REVIEW
Satoshi Kodera, Arihiro Kiyosue, Jiro Ando, Hiroshi Akazawa, Hiroyuki Morita, Masafumi Watanabe, Issei Komuro
The quality-adjusted life year (QALY) and incremental cost-effectiveness ratio (ICER) are important concepts in cost-effectiveness analysis, which is becoming increasingly important in Japan. QALY is used to estimate quality of life (QOL) and life years, and can be used to compare the efficacies of cancer and cardiovascular treatments. ICER is defined as the difference in cost between treatments divided by the difference in their effects, with a smaller ICER indicating better cost-effectiveness. Here, we present a review of cost-effectiveness analyses in Japan as well other countries...
December 12, 2017: International Heart Journal
https://www.readbyqxmd.com/read/29096860/current-insights-into-the-german-lipoprotein-apheresis-standard-pcsk9-inhibitors-lipoprotein-apheresis-or-both
#9
V J J Schettler, J Ringel, S Jacob, U Julius, R Klingel, F Heigl, E Roeseler, P Grützmacher
According to current European guidelines, lipid lowering therapy for progressive cardiovascular disease including cardiovascular events has to be focused on a target level for LDL-C. In contrast for Lp(a) a threshold has to be defined with respect to the method of measurement. However, due to new lipid lowering drug developments like PCSK9-inhibitors (PCSK-9-I) a therapeutic algorithm for patients with severe hypercholesterolemia or isolated Lipoprotein(a)-hyperlipoproteinemia with progressive cardiovascular disease may be necessary to manage the use of PCSK9-I, lipoprotein apheresis (LA) or both...
November 2017: Atherosclerosis. Supplements
https://www.readbyqxmd.com/read/29096851/how-effectively-will-pcsk9-inhibitors-allow-retrieval-of-freedom-from-apheresis-in-cardiovascular-high-risk-patients-estimates-form-a-large-single-center
#10
Bernd Hohenstein, Sergey Tselmin, Stefan R Bornstein, Ulrich Julius
Lipoprotein apheresis (LA) has been the last-resort therapeutic option in patients suffering from limited pharmaceutical options to lower highly elevated low density lipoprotein cholesterol (LDL-C) levels. Facing the introduction of the proprotein convertase subtilisin/kexine type 9 (PCSK-9) inhibitors, it has been speculated that they might replace LA to a large extend. Given an efficacy of approx. 55-65% to lower LDL-C it is important to analyze whether this might be realistic i) for potential candidates in apheresis sites and ii) for the future structures of the sites themselves...
November 2017: Atherosclerosis. Supplements
https://www.readbyqxmd.com/read/28994502/pro-protein-subtilisin-kexin-9-pcsk9-inhibition-in-practice-lipid-clinic-experience-in-2-contrasting-uk-centres
#11
Monika Kohli, Kinjal Patel, Zofia MacMahon, Radha Ramachandran, Martin A Crook, Timothy M Reynolds, Anthony S Wierzbicki
BACKGROUND: Prescribing criteria have been suggested for proprotein convertase subtilisin kexin-9 (PCSK-9) inhibitors but few studies exist of their real-world effectiveness. METHODS: This study audited PCSK-9 inhibitor therapy in 105 consecutive patients from two hospital centres-a university hospital (UH; n = 70) and a district general hospital (DGH; n = 35). Baseline characteristics including cardiovascular disease risk factors, NICE qualification criteria, efficacy and side effects were assessed...
November 2017: International Journal of Clinical Practice
https://www.readbyqxmd.com/read/28964708/ldl-apheresis-in-japan
#12
REVIEW
Hisashi Makino, Tamiko Tamanaha, Mariko Harada-Shiba
LDL apheresis has been developed as the treatment for refractory familial hypercholesterolemia (FH). Currently, plasma exchange, double membrane filtration, and selective LDL adsorption are available in Japan, and selective LDL adsorption is most common method. LDL apheresis can prevent atherosclerosis progression even in homozygous (HoFH). However, in our observational study, HoFH who started LDL apheresis from adulthood had poor prognosis compared with patients who started from childhood. Therefore, as far as possible, HoFH patients need to start LDL apheresis from childhood...
August 31, 2017: Transfusion and Apheresis Science
https://www.readbyqxmd.com/read/28854318/tying-reimbursement-to-outcomes-is-an-ideal-strategy-for-pcsk9-inhibitors
#13
Daniel M Blumenthal, Dana Goldman, Anupam B Jena
No abstract text is available yet for this article.
October 1, 2017: JAMA Cardiology
https://www.readbyqxmd.com/read/28831261/real-world-use-of-pcsk-9-inhibitors-by-early-adopters-cardiovascular-risk-factors-statin-co-treatment-and-short-term-adherence-in-routine-clinical-practice
#14
Kathleen A Fairman, Lindsay E Davis, David A Sclar
BACKGROUND: Inconsistency of real-world medication use with labeled indications may affect cost and clinical value of pharmacotherapy. PCSK-9 inhibitors are labeled in the US for use with statins to reduce low-density lipoprotein cholesterol in patients with atherosclerotic cardiovascular disease (ASCVD) or familial hypercholesterolemia (FH). OBJECTIVE: To assess consistency with labeled indications and treatment persistency for early (first 5 post-launch months) adopters of PCSK-9 inhibitor pharmacotherapy...
2017: Therapeutics and Clinical Risk Management
https://www.readbyqxmd.com/read/28777095/pcsk-9-gain-of-function-mutations-r496w-and-d374y-and-clinical-cardiovascular-characteristics-in-a-cohort-of-turkish-patients-with-familial-hypercholesterolemia
#15
Esra Kaya, Meral Kayıkçıoğlu, Aslı Tetik Vardarlı, Zuhal Eroğlu, Serdar Payzın, Levent Can
OBJECTIVE: The molecular basis of the mutations in the PCSK9 gene that produces familial hypercholesterolemia (FH) in the Turkish population is unknown. This study was conducted to determine the presence of four different PCSK9 gain-of-function (GOF) mutations (F216L, R496W, S127R, and D374Y) in a group of patients with FH. METHODS: A total of 80 consecutive patients with FH (mean age: 56±11 years; mean maximum LDL cholesterol: 251±76 mg/dL) were included in the study...
October 2017: Anatolian Journal of Cardiology
https://www.readbyqxmd.com/read/28709786/-pcsk-9-inhibitors-effects-on-ldl-c-and-future-implications-what-you-should-know
#16
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...
October 2017: Hipertensión y Riesgo Vascular
https://www.readbyqxmd.com/read/28555526/statin-intolerance-in-heterozygous-familial-hypercolesterolemia-with-cardiovascular-disease-after-pcsk-9-antibodies-what-else
#17
Francesco Sbrana, Beatrice Dal Pino, Federico Bigazzi, Andrea Ripoli, Claudio Passino, Alessandra Gabutti, Emilio M Pasanisi, Christina Petersen, Alessandro Valleggi, Giancarlo Todiere, Andrea Barison, Alberto Giannoni, Luca Panchetti, Francesco Becherini, Mascia Pianelli, Roberta Luciani, Tiziana Sampietro
Background Familial hypercholesterolemia is the elective clinical condition that deserves the maximal personalisation in lipid-lowering therapy, especially in the presence of statin intolerance. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors represent a promising approach to lower low-density lipoprotein (LDL) cholesterol. Methods We enrolled 18 patients (mean age 62 ± 8 years, 72% men) affected by heterozygous familial hypercholesterolemia and cardiovascular disease, with a history of statin intolerance assigned to PCSK9 inhibitors...
September 2017: European Journal of Preventive Cardiology
https://www.readbyqxmd.com/read/28500517/role-of-non-statins-ldl-c-thresholds-and-special-population-considerations-a-look-at-the-updated-2016-acc-consensus-committee-recommendations
#18
REVIEW
Bhavin B Adhyaru, Terry A Jacobson
PURPOSE OF REVIEW: The 2013 ACC/AHA Cholesterol guidelines was a major paradigm shift in the management and treatment of dyslipidemia. The new guidelines outlined "statin benefit groups," highlighted weighing the benefit versus risks of statin therapy ("net benefit"), and discussed the importance of shared decision making between patients and providers in primary prevention. While there was widespread agreement on the main groups benefiting from statin therapy, there was significant controversy regarding LDL-C goals and thresholds, the role of non-statin therapy, and the use of statins in specific populations...
June 2017: Current Atherosclerosis Reports
https://www.readbyqxmd.com/read/28471246/why-published-studies-of-the-cost-effectiveness-of-pcsk-9-inhibitors-yielded-such-markedly-different-results
#19
Peter P Toth, Warren Stevens, Jacquelyn W Chou
No abstract text is available yet for this article.
July 2017: Journal of Medical Economics
https://www.readbyqxmd.com/read/28456517/proprotein-convertase-inhibition-paralyzing-the-cell-s-master-switches
#20
REVIEW
Andres J Klein-Szanto, Daniel E Bassi
Proprotein convertases are serine proteases responsible for the cleavage and subsequent activation of protein substrates, many of them relevant for the development of an ample variety of diseases. Seven of the PCs, including furin and PACE4, recognize and hydrolyze the C-terminal end of the general sequence RXRR/KXR, whereas PCSK-9 recognizes a series of non-basic amino acids. In some systems, PC-mediated substrate activation results in the development of pathological processes, such as cancer, endocrinopathies, and cardiovascular and infectious diseases...
September 15, 2017: Biochemical Pharmacology
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