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Citations to this article

Secreted PCSK9 decreases the number of LDL receptors in hepatocytes and inlivers of parabiotic mice
Thomas A. Lagace, … , Robert E. Hammer, Jay D. Horton
Thomas A. Lagace, … , Robert E. Hammer, Jay D. Horton
Published November 1, 2006
Citation Information: J Clin Invest. 2006;116(11):2995-3005. https://doi.org/10.1172/JCI29383.
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Secreted PCSK9 decreases the number of LDL receptors in hepatocytes and inlivers of parabiotic mice

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Abstract

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a member of the proteinase K subfamily of subtilases that reduces the number of LDL receptors (LDLRs) in liver through an undefined posttranscriptional mechanism. We show that purified PCSK9 added to the medium of HepG2 cells reduces the number of cell-surface LDLRs in a dose- and time-dependent manner. This activity was approximately 10-fold greater for a gain-of-function mutant, PCSK9(D374Y), that causes hypercholesterolemia. Binding and uptake of PCSK9 were largely dependent on the presence of LDLRs. Coimmunoprecipitation and ligand blotting studies indicated that PCSK9 and LDLR directly associate; both proteins colocalized to late endocytic compartments. Purified PCSK9 had no effect on cell-surface LDLRs in hepatocytes lacking autosomal recessive hypercholesterolemia (ARH), an adaptor protein required for endocytosis of the receptor. Transgenic mice overexpressing human PCSK9 in liver secreted large amounts of the protein into plasma, which increased plasma LDL cholesterol concentrations to levels similar to those of LDLR-knockout mice. To determine whether PCSK9 was active in plasma, transgenic PCSK9 mice were parabiosed with wild-type littermates. After parabiosis, secreted PCSK9 was transferred to the circulation of wild-type mice and reduced the number of hepatic LDLRs to nearly undetectable levels. We conclude that secreted PCSK9 associates with the LDLR and reduces hepatic LDLR protein levels.

Authors

Thomas A. Lagace, David E. Curtis, Rita Garuti, Markey C. McNutt, Sahng Wook Park, Heidi B. Prather, Norma N. Anderson, Y.K. Ho, Robert E. Hammer, Jay D. Horton

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KH Cho, YJ Hong
The Korean Journal of Internal Medicine 2020
Non-hematopoietic deficiency of proprotein convertase subtilisin/kexin type 9 deficiency leads to more severe anemia in a murine model of sickle cell disease
J Venugopal, J Wang, C Guo, H Lu, YE Chen, DT Eitzman
Scientific Reports 2020
PCSK9 Inhibition: Insights From Clinical Trials and Future Prospects
JL Katzmann, I Gouni-Berthold, U Laufs
Frontiers in physiology 2020
A transient amphipathic helix in the prodomain of PCSK9 facilitates binding to low-density lipoprotein particles
SK Sarkar, AC Foo, A Matyas, I Asikhia, T Kosenko, NK Goto, A Vergara-Jaque, TA Lagace
The Journal of biological chemistry 2020
Sigma-2 Receptor—A Potential Target for Cancer/Alzheimer’s Disease Treatment via Its Regulation of Cholesterol Homeostasis
K Yang, C Zeng, C Wang, M Sun, D Yin, T Sun
Molecules (Basel, Switzerland) 2020
Genetic and In Vitro Inhibition of PCSK9 and Calcific Aortic Valve Stenosis
N Perrot, V Valerio, D Moschetta, SM Boekholdt, C Dina, HY Chen, E Abner, A Martinsson, HD Manikpurage, S Rigade, R Capoulade, E Mass, MA Clavel, TL Tourneau, D Messika-Zeitoun, NJ Wareham, JC Engert, G Polvani, P Pibarot, T Esko, JG Smith, P Mathieu, G Thanassoulis, JJ Schott, Y Bossé, M Camera, S Thériault, P Poggio, BJ Arsenault
JACC: Basic to Translational Science 2020
Elevated galectin-3 in women with gestational diabetes mellitus, a new surrogate for cardiovascular disease in women
Y Talmor-Barkan, C Chezar-Azerrad, B Kruchin, D Leshem-Lev, A Levi, E Hadar, R Kornowski, K Tenenbaum-Gavish, A Porter, FT Spradley
PloS one 2020
A New Liver Expression Quantitative Trait Locus Map From 1,183 Individuals Provides Evidence for Novel Expression Quantitative Trait Loci of Drug Response, Metabolic, and Sex‐Biased Phenotypes
AS Etheridge, PJ Gallins, D Jima, KA Broadaway, MJ Ratain, E Schuetz, E Schadt, A Schroder, C Molony, Y Zhou, KL Mohlke, FA Wright, F Innocenti
Clinical Pharmacology & Therapeutics 2020
Methotrexate Decreases the Level of PCSK9—A Novel Indicator of the Risk of Proatherogenic Lipid Profile in Psoriasis. The Preliminary Data
JA Krahel, A Baran, TW Kamiński, M Maciaszek, I Flisiak
Journal of Clinical Medicine 2020
PCSK9: A Key Target for the Treatment of Cardiovascular Disease (CVD)
Sobati S, Shakouri A, Edalati M, Mohammadnejad D, Parvan R, Masoumi J, Abdolalizadeh J
Advanced pharmaceutical bulletin 2020
Differential Effects of DPP-4 Inhibitors, Anagliptin and Sitagliptin, on PCSK9 Levels in Patients with Type 2 Diabetes Mellitus who are Receiving Statin Therapy
Furuhashi M, Sakuma I, Morimoto T, Higashiura Y, Sakai A, Matsumoto M, Sakuma M, Shimabukuro M, Nomiyama T, Arasaki O, Node K, Ueda S
Journal of Atherosclerosis and Thrombosis 2020
Identification of Novel Proteins Interacting with Proprotein Convertase Subtilisin/Kexin 9
Melendez QM, Wooten CJ, Krishnaji ST, Knagge K, Kirchner D, Lopez D
2020
A rapid strategy for screening high-efficiency PCSK9 inhibitors from Ginkgo biloba leaves by ligand fishing, HPLC-Q-TOF-MS and interdisciplinary assay
Li L, Fan ML, Li YN, Huang YX, Liu XF, Liu JH
Journal of Food and Drug Analysis 2020
Pressure overload leads to coronary plaque formation, progression and myocardial events in ApoE-/- mice
Alice Marino, Yi Zhang, Luisa Rubinelli, Maria Antonietta Riemma, James E. Ip, Annarita Di Lorenzo
JCI Insight 2019
The hepatic WASH complex is required for efficient plasma LDL and HDL cholesterol clearance
Melinde Wijers, Paolo Zanoni, Nalan Liv, Dyonne Y. Vos, Michelle Y Jäckstein, Marieke Smit, Sanne Wilbrink, Justina C. Wolters, Ydwine Y.T. van der Veen, N.C.A. Huijkman, Daphne Dekker, Niels J Kloosterhuis, Theo H. van Dijk, Daniel Billadeau, Folkert Kuipers, Judith Klumperman, Arnold von Eckardstein, Jan Albert Kuivenhoven, Bart van de Sluis
JCI Insight 2019
Mechanisms and regulation of cholesterol homeostasis
J Luo, H Yang, BL Song
Nature Reviews Molecular Cell Biology 2019
Anti-PCSK9 antibodies inhibit pro-atherogenic mechanisms in APOE*3Leiden.CETP mice
S Schuster, S Rubil, M Endres, HM Princen, JN Boeckel, K Winter, C Werner, U Laufs
Scientific Reports 2019
Hydrogen sulfide inhibits PCSK9 expression through the PI3K/Akt‑SREBP‑2 signaling pathway to influence lipid metabolism in HepG2 cells
J Xiao, XQ Bai, L Liao, M Zhou, J Peng, Q Xiang, Z Ren, HY Wen, ZS Jiang, ZH Tang, MM Wang, LS Liu
International journal of molecular medicine 2019
PCSK9 is Expressed in Human Visceral Adipose Tissue and Regulated by Insulin and Cardiac Natriuretic Peptides
M Bordicchia, F Spannella, G Ferretti, T Bacchetti, A Vignini, CD Pentima, L Mazzanti, R Sarzani
International journal of molecular sciences 2019
Biological Characterization of Computationally Designed Analogs of peptide TVFTSWEEYLDWV (Pep2-8) with Increased PCSK9 Antagonistic Activity
C Lammi, J Sgrignani, A Arnoldi, G Grazioso
Scientific Reports 2019
Lupin Peptide T9 (GQEQSHQDEGVIVR) Modulates the Mutant PCSK9D374Y Pathway: in vitro Characterization of its Dual Hypocholesterolemic Behavior
C Lammi, C Bollati, D Lecca, MP Abbracchio, A Arnoldi
Nutrients 2019
Cyclase-associated protein 1 is a binding partner of proprotein convertase subtilisin/kexin type-9 and is required for the degradation of low-density lipoprotein receptors by proprotein convertase subtilisin/kexin type-9
HD Jang, SE Lee, J Yang, HC Lee, D Shin, H Lee, J Lee, S Jin, S Kim, SJ Lee, J You, HW Park, KY Nam, SH Lee, SW Park, JS Kim, SY Kim, YW Kwon, SH Kwak, HM Yang, HS Kim
European Heart Journal 2019
Science, Serendipity and the Single Degree
Helen H. Hobbs
Journal of Clinical Investigation 2018
Sauchinone controls hepatic cholesterol homeostasis by the negative regulation of PCSK9 transcriptional network
HS Chae, BH You, DY Kim, H Lee, HW Ko, HJ Ko, YH Choi, SS Choi, YW Chin
Scientific Reports 2018
Discovery of Flavonoids from Scutellaria baicalensis with Inhibitory Activity Against PCSK 9 Expression: Isolation, Synthesis and Their Biological Evaluation
P Nhoek, HS Chae, J Masagalli, K Mailar, P Pel, YM Kim, W Choi, YW Chin
Molecules (Basel, Switzerland) 2018
Evolocumab: Considerations for the Management of Hyperlipidemia
BS Wiggins, J Senfield, H Kassahun, A Lira, R Somaratne
Current Atherosclerosis Reports 2018
Inactivation of the E3 Ubiquitin Ligase IDOL (Inducible Degrader of the Low-Density Lipoprotein Receptor) Attenuates Diet-Induced Obesity and Metabolic Dysfunction in Mice
NM van Loon, R Ottenhoff, S Kooijman, M Moeton, S Scheij, RL Abbing, MJ Gijbels, JH Levels, V Sorrentino, JF Berbée, PC Rensen, N Zelcer
Arteriosclerosis, thrombosis, and vascular biology 2018
Study on Regulation of Low Density Lipoprotein Cholesterol Metabolism using PCSK9 Gene Silencing: A computational Approach
B Vijayaraghavan, K Danabal, G Padmanabhan, K Ramanathan
Bioinformation 2018
A New Strategy for Rapidly Screening Natural Inhibitors Targeting the PCSK9/LDLR Interaction In Vitro
L Li, C Shen, YX Huang, YN Li, XF Liu, XM Liu, JH Liu
Molecules (Basel, Switzerland) 2018
Hepatocellular carcinoma-associated hypercholesterolemia: involvement of proprotein-convertase-subtilisin-kexin type-9 (PCSK9)
D Athavale, S Chouhan, V Pandey, SS Mayengbam, S Singh, MK Bhat
Cancer & Metabolism 2018
Cell-associated heparin-like molecules modulate the ability of LDL to regulate PCSK9 uptake
AM Galvan, JS Chorba
Journal of lipid research 2018
Inhibition of PCSK9 D374Y /LDLR Protein–Protein Interaction by Computationally Designed T9 Lupin Peptide
C Lammi, J Sgrignani, G Roda, A Arnoldi, G Grazioso
ACS Medicinal Chemistry Letters 2018
PCSK9 inhibition for primary prevention of ischaemic heart disease in heterozygous familial hypercholesterolaemia
Ryan A, Nevitt SJ, Byrne CD, Cook P
The Cochrane Database of Systematic Reviews 2018
Sortilin and Its Multiple Roles in Cardiovascular and Metabolic DiseasesHighlights
C Goettsch, M Kjolby, E Aikawa
Arteriosclerosis, thrombosis, and vascular biology 2017
ANGPTL8 negatively regulates NF-κB activation by facilitating selective autophagic degradation of IKKγ
Y Zhang, X Guo, W Yan, Y Chen, M Ke, C Cheng, X Zhu, W Xue, Q Zhou, L Zheng, S Wang, B Wu, X Liu, L Ma, L Huang, K Huang
Nature Communications 2017
APP, APLP2 and LRP1 interact with PCSK9 but are not required for PCSK9-mediated degradation of the LDLR in vivo
T Fu, YY Guan, J Xu, Y Wang
Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids 2017
Pro-inflammation NF-κB signaling triggers a positive feedback via enhancing cholesterol accumulation in liver cancer cells
M He, W Zhang, Y Dong, L Wang, T Fang, W Tang, B Lv, G Chen, B Yang, P Huang, J Xia
Journal of Experimental & Clinical Cancer Research 2017
Expression of SREBP-1c Requires SREBP-2-mediated Generation of a Sterol Ligand for LXR in Livers of Mice
S Rong, VA Cortés, S Rashid, NN Anderson, JG McDonald, G Liang, YA Moon, RE Hammer, JD Horton
eLife 2017
PCSK9 signaling pathways and their potential importance in clinical practice
M Wiciński, J Żak, B Malinowski, G Popek, G Grześk
The EPMA Journal 2017
Actinidia chinensis Planch root extract inhibits cholesterol metabolism in hepatocellular carcinoma through upregulation of PCSK9
M He, J Hou, L Wang, M Zheng, T Fang, X Wang, J Xia
Oncotarget 2017
Comparing expression and activity of PCSK9 in SPRET/EiJ and C57BL/6J mouse strains shows lack of correlation with plasma cholesterol
F Sirois, M Chrétien, M Mbikay
Molecular Genetics and Metabolism Reports 2017
Selective stalling of human translation through small-molecule engagement of the ribosome nascent chain
NG Lintner, KF McClure, D Petersen, AT Londregan, DW Piotrowski, L Wei, J Xiao, M Bolt, PM Loria, B Maguire, KF Geoghegan, A Huang, T Rolph, S Liras, JA Doudna, RG Dullea, JH Cate, C Khosla
PLoS Biology 2017
Genetic Architecture of Familial Hypercholesterolaemia
M Sharifi, M Futema, D Nair, SE Humphries
Current Cardiology Reports 2017
News on the molecular regulation and function of hepatic low-density lipoprotein receptor and LDLR-related protein 1:
B de Sluis, M Wijers, J Herz
Current Opinion in Lipidology 2017
Hepatitis C virus and proprotein convertase subtilisin/kexin type 9: a detrimental interaction to increase viral infectivity and disrupt lipid metabolism
M Pirro, V Bianconi, D Francisci, E Schiaroli, F Bagaglia, A Sahebkar, F Baldelli
Journal of Cellular and Molecular Medicine 2017
Low PCSK9 levels are correlated with mortality in patients with end-stage liver disease
V Schlegel, T Treuner-Kaueroff, D Seehofer, T Berg, S Becker, U Ceglarek, J Thiery, T Kaiser, MC Vinci
PloS one 2017
Increased half-life and enhanced potency of Fc-modified human PCSK9 monoclonal antibodies in primates
Y Shen, H Li, L Zhao, G Li, B Chen, Q Guo, B Gao, J Wu, T Yang, L Jin, Y Su, N Ferri
PloS one 2017
Treatment-Induced Viral Cure of Hepatitis C Virus-Infected Patients Involves a Dynamic Interplay among three Important Molecular Players in Lipid Homeostasis: Circulating microRNA (miR)-24, miR-223, and Proprotein Convertase Subtilisin/Kexin Type 9
A Hyrina, AD Olmstead, P Steven, M Krajden, E Tam, F Jean
EBioMedicine 2017
Cell-based, bioluminescent assay for monitoring the interaction between PCSK9 and the LDL receptor
SJ Duellman, T Machleidt, JJ Cali, J Vidugiriene
Journal of lipid research 2017
Inhibition of PCSK9 does not improve lipopolysaccharide-induced mortality in mice
JM Berger, AL Valdes, J Gromada, N Anderson, JD Horton
Journal of lipid research 2017
Association and differences in genetic polymorphisms in PCSK9 gene in subjects with lacunar infarction in the Han and Uygur populations of Xinjiang Uygur Autonomous Region of China
D Han, J Ma, C Hao, TuerhongTuerxun, L Du, X Zhang
NEURAL REGEN RES 2017
The PCSK9 revolution and the potential of PCSK9-based therapies to reduce LDL-cholesterol
NG Seidah
Global Cardiology Science and Practice 2017
How multi-scale structural biology elucidated context-dependent variability in ectodomain conformation along with the ligand capture and release cycle for LDLR family members
T Nogi
Biophysical Reviews 2017
Stepwise processing analyses of the single-turnover PCSK9 protease reveal its substrate sequence specificity and link clinical genotype to lipid phenotype
JS Chorba, AM Galvan, KM Shokat
The Journal of biological chemistry 2017
A New Approach to PCSK9 Therapeutics
N Wang, AR Tall
Circulation research 2017
A phase 1 study to evaluate the safety and LDL cholesterol-lowering effects of RG7652, a fully human monoclonal antibody against proprotein convertase subtilisin/kexin type 9: RG7652, an anti-PCSK9 antibody, reduces LDL-C
A Baruch, D Luca, RS Kahn, KJ Cowan, M Leabman, NR Budha, CP Chiu, Y Wu, D Kirchhofer, A Peterson, JC Davis, WG Tingley
Clinical Cardiology 2017
CAT-2003: A novel sterol regulatory element-binding protein inhibitor that reduces steatohepatitis, plasma lipids, and atherosclerosis in apolipoprotein E*3-Leiden mice: Zimmer et al
M Zimmer, P Bista, EL Benson, DY Lee, F Liu, D Picarella, RB Vega, CB Vu, M Yeager, M Ding, G Liang, JD Horton, R Kleemann, T Kooistra, MC Morrison, PY Wielinga, JC Milne, MR Jirousek, AJ Nichols
Hepatology Communications 2017
Circulating PCSK9 is lowered acutely following surgery
Druce I, Abujrad H, Chaker S, Meggison H, Hill A, Raymond A, Mayne J, Ooi TC
Journal of Clinical Laboratory Analysis 2017
Dysregulation of the Low-Density Lipoprotein Receptor Pathway Is Involved in Lipid Disorder-Mediated Organ Injury
Y Zhang, KL Ma, XZ Ruan, BC Liu
International journal of biological sciences 2016
CCC- and WASH-mediated endosomal sorting of LDLR is required for normal clearance of circulating LDL
P Bartuzi, DD Billadeau, R Favier, S Rong, D Dekker, A Fedoseienko, H Fieten, M Wijers, JH Levels, N Huijkman, N Kloosterhuis, H der Molen, G Brufau, AK Groen, AM Elliott, JA Kuivenhoven, B Plecko, G Grangl, J McGaughran, JD Horton, E Burstein, MH Hofker, B de Sluis
Nature Communications 2016
Disorders of lipid metabolism in nephrotic syndrome: mechanisms and consequences
ND Vaziri
Kidney International 2016
Human PCSK9 promotes hepatic lipogenesis and atherosclerosis development via apoE- and LDLR-mediated mechanisms
H Tavori, I Giunzioni, IM Predazzi, D Plubell, A Shivinsky, J Miles, RM Devay, H Liang, S Rashid, MR Linton, S Fazio
Cardiovascular Research 2016
Precise regulation of the guidance receptor DMA-1 by KPC-1/Furin instructs dendritic branching decisions: ( A ) Fluorescent images showing (red) morphology of the PVD neuron, (green) localization of SAX-7 in the hypodermal cell, (blue) seam cells and overlay between the three in wild-type worms. SAX-7 was enriched in two sublateral longitudinal lines and at the lateral midline around the seam cell-hypodermal junctions. Arrows: Sublateral stripes of enriched SAX-7 that co-localize with PVD 3° dendrites. Arrowhead: SAX-7 enriched near the 1°dendrites, where it was encountered by the 2° branches as they emerge. The images in the lower panels are zoomed-in views of the regions indicated by the boxes. Dotted lines indicate the 'trap zone' marked by enriched SAX-7 around seam cells. ( B ) In kpc-1(gk8) mutants, almost all branches failed to grow out of the trap zone between the dotted lines indicated by enriched SAX-7. Scale bar: 10 μm. ( C ) Quantification of the percentage of 2° branches trapped around the 1°dendrite. *** is p0.05 by Student’s T-test. N=50 for each genotype
X Dong, H Chiu, YJ Park, W Zou, Y Zou, E Özkan, C Chang, K Shen
eLife 2016
Lupin Peptides Modulate the Protein-Protein Interaction of PCSK9 with the Low Density Lipoprotein Receptor in HepG2 Cells
C Lammi, C Zanoni, G Aiello, A Arnoldi, G Grazioso
Scientific Reports 2016
Polydatin ameliorates lipid and glucose metabolism in type 2 diabetes mellitus by downregulating proprotein convertase subtilisin/kexin type 9 (PCSK9)
Y Wang, J Ye, J Li, C Chen, J Huang, P Liu, H Huang
Cardiovascular Diabetology 2016
Effects of Statin Therapy on Plasma Proprotein Convertase Subtilisin/kexin Type 9 and Sortilin Levels in Statin-Naive Patients with Coronary Artery Disease
T Nozue, H Hattori, K Ogawa, T Kujiraoka, T Iwasaki, I Michishita
Journal of Atherosclerosis and Thrombosis 2016
Tanshinone IIA Modulates Low Density Lipoprotein Uptake via Down-Regulation of PCSK9 Gene Expression in HepG2 Cells
HC Chen, PY Chen, MJ Wu, MH Tai, JH Yen, MC Vinci
PloS one 2016
The Loss and Gain of Functional Amino Acid Residues Is a Common Mechanism Causing Human Inherited Disease
J Lugo-Martinez, V Pejaver, KA Pagel, S Jain, M Mort, DN Cooper, SD Mooney, P Radivojac, Y Bromberg
PLoS computational biology 2016
Trafficking Dynamics of PCSK9-Induced LDLR Degradation: Focus on Human PCSK9 Mutations and C-Terminal Domain
S Poirier, HA Hamouda, L Villeneuve, A Demers, G Mayer, M Kanzaki
PloS one 2016
Lipopolysaccharide Is Cleared from the Circulation by Hepatocytes via the Low Density Lipoprotein Receptor
E Topchiy, M Cirstea, HJ Kong, JH Boyd, Y Wang, JA Russell, KR Walley, I Tancevski
PloS one 2016
Alirocumab, a Therapeutic Human Antibody to PCSK9, Does Not Affect CD81 Levels or Hepatitis C Virus Entry and Replication into Hepatocytes
A Ramanathan, V Gusarova, N Stahl, A Gurnett-Bander, CA Kyratsous, EI PECHEUR
PloS one 2016
PCSK9 inhibition: the dawn of a new age in cholesterol lowering?
D Preiss, M Mafham
Diabetologia 2016
Studies of the autoinhibitory segment comprising residues 31–60 of the prodomain of PCSK9: Possible implications for the mechanism underlying gain-of-function mutations
L Wierød, J Cameron, TB Strøm, TP Leren
Molecular Genetics and Metabolism Reports 2016
Point mutations at the catalytic site of PCSK9 inhibit folding, autoprocessing, and interaction with the LDL receptor: PCSK9 Autoprocessing and Inhibition by Mutations
CW Garvie, CV Fraley, NH Elowe, EK Culyba, CT Lemke, BK Hubbard, VK Kaushik, DS Daniels
Protein Science 2016
Identification of roles for H264, H306, H439, and H635 in acid-dependent lipoprotein release by the LDL receptor
H Dong, Z Zhao, DG LeBrun, P Michaely
Journal of lipid research 2016
Endoplasmic Reticulum Stress and Ca 2+ Depletion Differentially Modulate the Sterol Regulatory Protein PCSK9 to Control Lipid Metabolism
P Lebeau, A Al-Hashimi, S Sood, Š Lhoták, P Yu, G Gyulay, G Paré, SR Chen, B Trigatti, A Prat, NG Seidah, RC Austin
The Journal of biological chemistry 2016
Population Pharmacokinetics (PK) and Pharmacodynamics (PD) Analysis of LY3015014, a Monoclonal Antibody to Protein Convertase Subtilisin/Kexin Type 9 (PCSK9) in Healthy Subjects and Hypercholesterolemia Patients.
Shen T, James DE, Krueger KA
Pharmaceutical Research 2016
Hypercholesterolemia, low density lipoprotein receptor and proprotein convertase subtilisin/kexin-type 9
Hong-Mei Gu, Da-Wei Zhang
Journal of Biomedical Research 2015
The Promise of Proprotein Convertase Subtilisin/Kexin 9 Inhibitors for the Treatment of Familial Hypercholesterolemia
Y Pokharel, SS Virani, CM Ballantyne
Current Atherosclerosis Reports 2015
A Century of Cholesterol and Coronaries: From Plaques to Genes to Statins
JL Goldstein, MS Brown
Cell 2015
Impacts of ezetimibe on PCSK9 in rats: study on the expression in different organs and the potential mechanisms
RX Xu, J Liu, XL Li, S Li, Y Zhang, YJ Jia, J Sun, JJ Li
Journal of Translational Medicine 2015
Hemodynamic Shear Stress via ROS Modulates PCSK9 Expression in Human Vascular Endothelial and Smooth Muscle Cells and Along the Mouse Aorta
Z Ding, S Liu, X Wang, X Deng, Y Fan, C Sun, Y Wang, JL Mehta
Antioxidants & Redox Signaling 2015
Lipoprotein(a) Catabolism Is Regulated by Proprotein Convertase Subtilisin/Kexin Type 9 through the Low Density Lipoprotein Receptor
R Romagnuolo, CA Scipione, MB Boffa, SM Marcovina, NG Seidah, ML Koschinsky
The Journal of biological chemistry 2015
Common Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Epitopes Mediate Multiple Routes for Internalization and Function
RM DeVay, L Yamamoto, DL Shelton, H Liang, MC Vinci
PloS one 2015
β-Estradiol results in a proprotein convertase subtilisin/kexin type 9-dependent increase in low-density lipoprotein receptor levels in human hepatic HuH7 cells
AE Starr, V Lemieux, J Noad, JI Moore, T Dewpura, A Raymond, M Chrétien, D Figeys, J Mayne
FEBS Journal 2015
Amyloid Precursor-like Protein 2 and Sortilin Do Not Regulate the PCSK9 Convertase-mediated Low Density Lipoprotein Receptor Degradation but Interact with Each Other
C Butkinaree, M Canuel, R Essalmani, S Poirier, S Benjannet, MC Asselin, A Roubtsova, J Hamelin, J Marcinkiewicz, A Chamberland, J Guillemot, G Mayer, SS Sisodia, Y Jacob, A Prat, NG Seidah
The Journal of biological chemistry 2015
Lipid-Lowering Drug Therapy for CVD Prevention: Looking into the Future
EA Stein, FJ Raal
Current Cardiology Reports 2015
Decreased PCSK9 expression in human hepatocellular carcinoma
M Bhat, N Skill, V Marcus, M Deschenes, X Tan, J Bouteaud, S Negi, Z Awan, R Aikin, J Kwan, R Amre, S Tabaries, M Hassanain, NG Seidah, M Maluccio, P Siegel, P Metrakos
BMC Gastroenterology 2015
Lipid levels in HIV-positive men receiving anti-retroviral therapy are not associated with copy number variation of reverse cholesterol transport pathway genes
RB Marino, LA Kingsley, SK Hussain, JH Bream, S Penogonda, P Duggal, JJ Martinson
BMC Research Notes 2015
The Influence of OLR1 and PCSK9 Gene Polymorphisms on Ischemic Stroke: Evidence from a Meta-Analysis
A Au, LR Griffiths, KK Cheng, CW Kooi, L Irene, LK Wei
Scientific Reports 2015
Plasma Membrane Tetraspanin CD81 Complexes with Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) and Low Density Lipoprotein Receptor (LDLR), and Its Levels Are Reduced by PCSK9
QT Le, M Blanchet, NG Seidah, P Labonté
The Journal of biological chemistry 2015
PCSK9 and triglyceride-rich lipoprotein metabolism
Druce I, Abujrad H, Ooi TC
Journal of Biomedical Research 2015
PCSK9 and LDLR degradation: regulatory mechanisms in circulation and in cells
TA Lagace
Current Opinion in Lipidology 2014
The Sirt1 activator SRT3025 provides atheroprotection in Apoe-/- mice by reducing hepatic Pcsk9 secretion and enhancing Ldlr expression
MX Miranda, LJ van Tits, C Lohmann, T Arsiwala, S Winnik, A Tailleux, S Stein, AP Gomes, V Suri, JL Ellis, TA Lutz, MO Hottiger, DA Sinclair, J Auwerx, K Schoonjans, B Staels, TF Luscher, CM Matter
European Heart Journal 2014
Efficacy and Safety of Alirocumab in Patients with Heterozygous Familial Hypercholesterolemia not Adequately Controlled with Current Lipid-Lowering Therapy: Design and Rationale of the ODYSSEY FH Studies
JJ Kastelein, JG Robinson, M Farnier, M Krempf, G Langslet, C Lorenzato, DA Gipe, MT Baccara-Dinet
Cardiovascular Drugs and Therapy 2014
Lipid lowering with PCSK9 inhibitors
RT Dadu, CM Ballantyne
Nature Reviews Cardiology 2014
Effect of E670G Polymorphism in PCSK9 Gene on the Risk and Severity of Coronary Heart Disease and Ischemic Stroke in a Tunisian Cohort
A Slimani, Y Harira, I Trabelsi, W Jomaa, F Maatouk, KB Hamda, MN Slimane
Journal of Molecular Neuroscience 2014
Living the PCSK9 Adventure: from the Identification of a New Gene in Familial Hypercholesterolemia Towards a Potential New Class of Anticholesterol Drugs
M Abifadel, S Elbitar, PE Khoury, Y Ghaleb, M Chémaly, ML Moussalli, JP Rabès, M Varret, C Boileau
Current Atherosclerosis Reports 2014
Alirocumab inhibits atherosclerosis, improves the plaque morphology, and enhances the effects of a statin
S Kuhnast, JW van der Hoorn, EJ Pieterman, AM van Hoek, WJ Sasiela, V Gusarova, A Peyman, HL Schafer, U Schwahn, JW Jukema, HM Princen
Journal of lipid research 2014
PCSK9 is a critical regulator of the innate immune response and septic shock outcome
KR Walley, KR Thain, JA Russell, MP Reilly, NJ Meyer, JF Ferguson, JD Christie, T Nakada, CD Fjell, SA Thair, MS Cirstea, JH Boyd
Science Translational Medicine 2014
Correlation of PCSK9 Gene Polymorphism with Cerebral Ischemic Stroke in Xinjiang Han and Uygur Populations
J Lei
Medical science monitor : international medical journal of experimental and clinical research 2014
Relation of plasma PCSK9 levels to lipoprotein subfractions in patients with stable coronary artery disease
RX Xu, S Li, Y Zhang, XL Li, YL Guo, CG Zhu, JJ Li
Lipids in Health and Disease 2014
The Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Active Site and Cleavage Sequence Differentially Regulate Protein Secretion from Proteolysis
JS Chorba, KM Shokat
The Journal of biological chemistry 2014
Annexin A2 Reduces PCSK9 Protein Levels via a Translational Mechanism and Interacts with the M1 and M2 Domains of PCSK9
K Ly, YG Saavedra, M Canuel, S Routhier, R Desjardins, J Hamelin, J Mayne, C Lazure, NG Seidah, R Day
The Journal of biological chemistry 2014
Isolation and characterization of the circulating truncated form of PCSK9
B Han, PI Eacho, MD Knierman, JS Troutt, RJ Konrad, X Yu, KM Schroeder
Journal of lipid research 2014
Proprotein convertase subtilisin/kexin type 9 expression is transiently up-regulated in the acute period of myocardial infarction in rat
Y Zhang, J Liu, S Li, RX Xu, J Sun, Y Tang, JJ Li
BMC Cardiovascular Disorders 2014
PCSK9 inhibition fails to alter hepatic LDLR, circulating cholesterol, and atherosclerosis in the absence of ApoE
B Ason, JW van der Hoorn, J Chan, E Lee, EJ Pieterman, KK Nguyen, M Di, S Shetterly, J Tang, WC Yeh, M Schwarz, JW Jukema, R Scott, SM Wasserman, HM Princen, S Jackson
Journal of lipid research 2014
PCSK9 is present in human cerebrospinal fluid and is maintained at remarkably constant concentrations throughout the course of the day.
Chen YQ, Troutt JS, Konrad RJ
Lipids 2014
FoxO3 transcription factor and Sirt6 deacetylase regulate low density lipoprotein (LDL)-cholesterol homeostasis via control of the proprotein convertase subtilisin/kexin type 9 (Pcsk9) gene expression
R Tao, X Xiong, RA DePinho, CX Deng, XC Dong
The Journal of biological chemistry 2013
Low density lipoprotein binds to proprotein convertase subtilisin/kexin type-9 (PCSK9) in human plasma and inhibits PCSK9-mediated low density lipoprotein receptor degradation
T Kosenko, M Golder, G Leblond, W Weng, TA Lagace
The Journal of biological chemistry 2013
The biology of PCSK9 from the endoplasmic reticulum to lysosomes: new and emerging therapeutics to control low-density lipoprotein cholesterol
S Poirier, G Mayer
Drug design, development and therapy 2013
Internalized PCSK9 dissociates from recycling LDL receptors in PCSK9-resistant SV-589 fibroblasts
MA Nguyen, T Kosenko, TA Lagace
Journal of lipid research 2013
Human Serum PCSK9 Is Elevated at Parturition in Comparison to Nonpregnant Subjects While Serum PCSK9 from Umbilical Cord Blood is Lower Compared to Maternal Blood
P Peticca, A Raymond, A Gruslin, M Cousins, E Adetola, H Abujrad, J Mayne, TC Ooi
ISRN Endocrinology 2013
Proprotein convertase subtilisin/kexin type 9 (PCSK9) can mediate degradation of the low density lipoprotein receptor-related protein 1 (LRP-1)
M Canuel, X Sun, MC Asselin, E Paramithiotis, A Prat, NG Seidah
PloS one 2013
Differential effects of PCSK9 loss of function variants on serum lipid and PCSK9 levels in Caucasian and African Canadian populations
J Mayne, TC Ooi, A Raymond, M Cousins, L Bernier, T Dewpura, F Sirois, M Mbikay, J Davignon, M Chrétien
Lipids in Health and Disease 2013
Opening up new fronts in the fight against cholesterol
RA Debose-Boyd, JD Horton
eLife 2013
PCSK9-mediated degradation of the LDL receptor generates a 17 kDa C-terminal LDL receptor fragment
K Tveten, TB Strøm, KE Berge, TP Leren
Journal of lipid research 2013
Characterization of proprotein convertase subtilisin/kexin type 9 (PCSK9) trafficking reveals a novel lysosomal targeting mechanism via amyloid precursor-like protein 2 (APLP2)
RM DeVay, DL Shelton, H Liang
The Journal of biological chemistry 2013
IDOL stimulates clathrin-independent endocytosis and multivesicular body-mediated lysosomal degradation of the low-density lipoprotein receptor
E Scotti, M Calamai, CN Goulbourne, L Zhang, C Hong, RR Lin, J Choi, PF Pilch, LG Fong, P Zou, AY Ting, FS Pavone, SG Young, P Tontonoz
Molecular and cellular biology 2013
Characterization of the role of EGF-A of low density lipoprotein receptor in PCSK9 binding
H Gu, A Adijiang, M Mah, D Zhang
Journal of lipid research 2013
Elevated PCSK9 Levels in Untreated Patients With Heterozygous or Homozygous Familial Hypercholesterolemia and the Response to High‐Dose Statin Therapy
F Raal, V Panz, A Immelman, G Pilcher
Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease 2013
Serum Proprotein Convertase Subtilisin/Kexin Type 9 and Cell Surface Low-Density Lipoprotein Receptor: Evidence for a Reciprocal Regulation
H Tavori, D Fan, JL Blakemore, PG Yancey, L Ding, MR Linton, S Fazio
Circulation 2013
Potential of proprotein convertase subtilisin/kexin type 9 based therapeutics.
Stein EA, Swergold GD
Current Atherosclerosis Reports 2013
The Xbp1s-GalE Axis links ER Stress to Postprandial Hepatic Metabolism
Yingfeng Deng, Zhao V. Wang, Caroline Tao, Ningguo Gao, William L. Holland, Anwarul Ferdous, Joyce J. Repa, Guosheng Liang, Jin Ye, Mark A. Lehrman, Joseph A. Hill, Jay D. Horton, Philipp E. Scherer
Journal of Clinical Investigation 2012
An Anti-PCSK9 Antibody Reduces LDL-Cholesterol On Top Of A Statin And Suppresses Hepatocyte SREBP-Regulated Genes
L Zhang, T McCabe, JH Condra, YG Ni, LB Peterson, W Wang, AM Strack, F Wang, S Pandit, H Hammond, D Wood, D Lewis, R Rosa, V Mendoza, AM Cumiskey, DG Johns, BC Hansen, X Shen, N Geoghagen, K Jensen, L Zhu, K Wietecha, D Wisniewski, L Huang, JZ Zhao, R Ernst, R Hampton, P Haytko, F Ansbro, S Chilewski, J Chin, LJ Mitnaul, A Pellacani, CP Sparrow, Z An, W Strohl, B Hubbard, AS Plump, D Blom, A Sitlani
International journal of biological sciences 2012
Blockade of cholesterol absorption by ezetimibe reveals a complex homeostatic network in enterocytes
LJ Engelking, MR McFarlane, CK Li, G Liang
Journal of lipid research 2012
Molecular characterization of proprotein convertase subtilisin/kexin type 9-mediated degradation of the LDLR
Y Wang, Y Huang, HH Hobbs, JC Cohen
Journal of lipid research 2012
Lowering Plasma Cholesterol by Raising LDL Receptors — Revisited
SG Young, LG Fong
New England Journal of Medicine 2012
Peroxisome Proliferator-activated receptor γ activation by ligands and dephosphorylation induces proprotein convertase subtilisin kexin type 9 and low density lipoprotein receptor expression
Y Duan, Y Chen, W Hu, X Li, X Yang, X Zhou, Z Yin, D Kong, Z Yao, DP Hajjar, L Liu, Q Liu, J Han
The Journal of biological chemistry 2012
c-IAP1 Binds and Processes PCSK9 Protein: Linking the c-IAP1 in a TNF-α Pathway to PCSK9-Mediated LDLR Degradation Pathway
W Xu, L Liu, D Hornby
Molecules (Basel, Switzerland) 2012
Proprotein convertase subtilisin/kexin type 9: from the discovery to the development of new therapies for cardiovascular diseases
N Ferri
Scientifica 2012
Utilizing HaloTag Technology to Track the Fate of PCSK9 from Intracellular vs. Extracellular Sources
X Ai, P Fischer, OC Palyha, D Wisniewski, B Hubbard, K Akinsanya, AM Strack, AG Ehrhardt
Current chemical genomics 2012
Loss- and gain-of-function PCSK9 variants: cleavage specificity, dominant negative effects, and low density lipoprotein receptor (LDLR) degradation
S Benjannet, J Hamelin, M Chrétien, NG Seidah
The Journal of biological chemistry 2012
The PCSK9 decade
G Lambert, B Sjouke, B Choque, JJ Kastelein, GK Hovingh
Journal of lipid research 2012
Immunization against proprotein convertase subtilisin-like/kexin type 9 lowers plasma LDL-cholesterol levels in mice
E Fattori, M Cappelletti, PL Surdo, A Calzetta, C Bendtsen, YG Ni, S Pandit, A Sitlani, G Mesiti, A Carfí, P Monaci
Journal of lipid research 2012
Regulation of epithelial sodium channel trafficking by proprotein convertase subtilisin/kexin type 9 (PCSK9)
V Sharotri, DM Collier, DR Olson, R Zhou, PM Snyder
The Journal of biological chemistry 2012
Feedback Regulation of Cholesterol Uptake by the LXR-IDOL-LDLR Axis
L Zhang, K Reue, LG Fong, SG Young, P Tontonoz
Arteriosclerosis, thrombosis, and vascular biology 2012
Low Prevalence of Mutations in Known Loci for Autosomal Dominant Hypercholesterolemia in a Multiethnic Patient Cohort
Z Ahmad, B Adams-Huet, C Chen, A Garg
Circulation. Cardiovascular genetics 2012
Effects of currently prescribed LDL-C-lowering drugs on PCSK9 and implications for the next generation of LDL-C-lowering agents
RJ Konrad, JS Troutt, G Cao
Lipids in Health and Disease 2011
Mechanistic implications for LDL receptor degradation from the PCSK9/LDLR structure at neutral pH
PL Surdo, MJ Bottomley, A Calzetta, EC Settembre, A Cirillo, S Pandit, YG Ni, B Hubbard, A Sitlani, A Carfí
EMBO reports 2011
Role of an Intramolecular Contact on Lipoprotein Uptake by the LDL Receptor
Z Zhao, P Michaely
Biochimica et Biophysica Acta 2011
Improved efficacy for ezetimibe and rosuvastatin by attenuating the induction of PCSK9[S]
B Ason, S Tep, HR Davis, Y Xu, G Tetzloff, B Galinski, F Soriano, N Dubinina, L Zhu, A Stefanni, KK Wong, M Tadin-Strapps, SR Bartz, B Hubbard, M Ranalletta, AB Sachs, WM Flanagan, A Strack, NA Kuklin
Journal of lipid research 2011
PCSK9 reduces the protein levels of the LDL receptor in mouse brain during development and after ischemic stroke[S]
E Rousselet, J Marcinkiewicz, J Kriz, A Zhou, ME Hatten, A Prat, NG Seidah
Journal of lipid research 2011
A PCSK9-binding antibody that structurally mimics the EGF(A) domain of LDL-receptor reduces LDL cholesterol in vivo1[S]
YG Ni, SD Marco, JH Condra, LB Peterson, W Wang, F Wang, S Pandit, HA Hammond, R Rosa, RT Cummings, DD Wood, X Liu, MJ Bottomley, X Shen, RM Cubbon, S Wang, DG Johns, C Volpari, L Hamuro, J Chin, L Huang, JZ Zhao, S Vitelli, P Haytko, D Wisniewski, LJ Mitnaul, CP Sparrow, B Hubbard, A Carfí, A Sitlani
Journal of lipid research 2011
Targeted Disruption of the Idol Gene Alters Cellular Regulation of the Low-Density Lipoprotein Receptor by Sterols and Liver X Receptor Agonists
E Scotti, C Hong, Y Yoshinaga, Y Tu, Y Hu, N Zelcer, R Boyadjian, PJ de Jong, SG Young, LG Fong, P Tontonoz
Molecular and cellular biology 2011
Structure-based kernels for the prediction of catalytic residues and their involvement in human inherited disease
F Xin, S Myers, YF Li, DN Cooper, SD Mooney, P Radivojac
Bioinformatics (Oxford, England) 2010
A proprotein convertase subtilisin-like/kexin type 9 (PCSK9) C-terminal domain antibody antigen-binding fragment inhibits PCSK9 internalization and restores low density lipoprotein uptake
YG Ni, JH Condra, L Orsatti, X Shen, SD Marco, S Pandit, MJ Bottomley, L Ruggeri, RT Cummings, RM Cubbon, JC Santoro, A Ehrhardt, D Lewis, TS Fisher, S Ha, L Njimoluh, DD Wood, HA Hammond, D Wisniewski, C Volpari, A Noto, PL Surdo, B Hubbard, A Carfí, A Sitlani
The Journal of biological chemistry 2010
Fenofibrate treatment increases human serum proprotein convertase subtilisin kexin type 9 levels
JS Troutt, WE Alborn, G Cao, RJ Konrad
Journal of lipid research 2010
A new method for measurement of total plasma PCSK9: clinical applications
G Dubuc, M Tremblay, G Paré, H Jacques, J Hamelin, S Benjannet, L Boulet, J Genest, L Bernier, NG Seidah, J Davignon
Journal of lipid research 2010
Genetics of lipid disorders
J Pirruccello, S Kathiresan
Current Opinion in Cardiology 2010
Effects of the Prosegment and pH on the Activity of PCSK9
S Benjannet, YG Saavedra, J Hamelin, MC Asselin, R Essalmani, A Pasquato, P Lemaire, G Duke, B Miao, F Duclos, R Parker, G Mayer, NG Seidah
The Journal of biological chemistry 2010
PCSK9 is not involved in the degradation of LDL receptors and BACE1 in the adult mouse brain
M Liu, G Wu, J Baysarowich, M Kavana, GH Addona, KK Bierilo, JS Mudgett, G Pavlovic, A Sitlani, JJ Renger, BK Hubbard, TS Fisher, CV Zerbinatti
Journal of lipid research 2010
High-dose atorvastatin causes a rapid sustained increase in human serum PCSK9 and disrupts its correlation with LDL cholesterol
G Welder, I Zineh, MA Pacanowski, JS Troutt, G Cao, RJ Konrad
Journal of lipid research 2010
A Two-step Binding Model of PCSK9 Interaction with the Low Density Lipoprotein Receptor*
T Yamamoto, C Lu, RO Ryan
The Journal of biological chemistry 2010
PCSK9 as a therapeutic target in atherosclerosis.
Marian AJ
Current Atherosclerosis Reports 2010
Pulmonary surfactant: an immunological perspective
ZC Chroneos, Z Sever-Chroneos, VL Shepherd
Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 2009
Molecular genetics of atherosclerosis
H Roy, S Bhardwaj, S Yla-Herttuala
Human Genetics 2009
Antagonism of secreted PCSK9 increases low density lipoprotein receptor expression in HepG2 cells
MC McNutt, HJ Kwon, C Chen, JR Chen, JD Horton, TA Lagace
The Journal of biological chemistry 2009
Antibody-mediated disruption of the interaction between PCSK9 and the low-density lipoprotein receptor
CJ Duff, MJ Scott, IT Kirby, SE Hutchinson, SL Martin, NM Hooper
Biochemical Journal 2009
Dissection of the endogenous cellular pathways of PCSK9-induced low density lipoprotein receptor degradation: evidence for an intracellular route
S Poirier, G Mayer, V Poupon, PS McPherson, R Desjardins, K Ly, MC Asselin, R Day, FJ Duclos, M Witmer, R Parker, A Prat, NG Seidah
The Journal of biological chemistry 2009
A proprotein convertase subtilisin/kexin type 9 neutralizing antibody reduces serum cholesterol in mice and nonhuman primates
JC Chan, DE Piper, Q Cao, D Liu, C King, W Wang, J Tang, Q Liu, J Higbee, Z Xia, Y Di, S Shetterly, Z Arimura, H Salomonis, WG Romanow, ST Thibault, R Zhang, P Cao, XP Yang, T Yu, M Lu, MW Retter, G Kwon, K Henne, O Pan, MM Tsai, B Fuchslocher, E Yang, L Zhou, KJ Lee, M Daris, J Sheng, Y Wang, WD Shen, WC Yeh, M Emery, NP Walker, B Shan, M Schwarz, SM Jackson
Proceedings of the National Academy of Sciences 2009
Function and distribution of circulating human PCSK9 expressed extrahepatically in transgenic mice
Y Luo, L Warren, D Xia, H Jensen, T Sand, S Petras, W Qin, KS Miller, J Hawkins
Journal of lipid research 2009
Genetic and Metabolic Determinants of Plasma PCSK9 Levels
SG Lakoski, TA Lagace, JC Cohen, JD Horton, HH Hobbs
The Journal of clinical endocrinology and metabolism 2009
Lipoproteins, cholesterol homeostasis and cardiac health.
Daniels TF, Killinger KM, Michal JJ, Wright RW Jr, Jiang Z
International journal of biological sciences 2009
Plasma PCSK9 preferentially reduces liver LDL receptors in mice
A Grefhorst, MC McNutt, TA Lagace, JD Horton
Journal of lipid research 2008
PCSK9 function and physiology
AS Peterson, LG Fong, SG Young
Journal of lipid research 2008
Regulation of ApoB secretion by the low density lipoprotein receptor requires exit from the endoplasmic reticulum and interaction with ApoE or ApoB
DA Blasiole, AT Oler, AD Attie
The Journal of biological chemistry 2008
Structural requirements for PCSK9-mediated degradation of the low-density lipoprotein receptor
DW Zhang, R Garuti, WJ Tang, JC Cohen, HH Hobbs
Proceedings of the National Academy of Sciences 2008
Mathematical model for low density lipoprotein (LDL) endocytosis by hepatocytes
JA Wattis, B O'Malley, H Blackburn, L Pickersgill, J Panovska, HM Byrne, KG Jackson
Bulletin of Mathematical Biology 2008
Therapeutic RNAi targeting PCSK9 acutely lowers plasma cholesterol in rodents and LDL cholesterol in nonhuman primates
M Frank-Kamenetsky, A Grefhorst, NN Anderson, TS Racie, B Bramlage, A Akinc, D Butler, K Charisse, R Dorkin, Y Fan, C Gamba-Vitalo, P Hadwiger, M Jayaraman, M John, KN Jayaprakash, M Maier, L Nechev, KG Rajeev, T Read, I Röhl, J Soutschek, P Tan, J Wong, G Wang, T Zimmermann, A Fougerolles, HP Vornlocher, R Langer, DG Anderson, M Manoharan, V Koteliansky, JD Horton, K Fitzgerald
Proceedings of the National Academy of Sciences 2008
Inflammation stimulates the expression of PCSK9
KR Feingold, AH Moser, JK Shigenaga, SM Patzek, C Grunfeld
Biochemical and Biophysical Research Communications 2008
Plasma PCSK9 levels are significantly modified by statins and fibrates in humans
J Mayne, T Dewpura, A Raymond, M Cousins, A Chaplin, KA Lahey, SA Lahaye, M Mbikay, TC Ooi, M Chrétien
Lipids in Health and Disease 2008
Molecular basis for LDL receptor recognition by PCSK9
HJ Kwon, TA Lagace, MC McNutt, JD Horton, J Deisenhofer
Proceedings of the National Academy of Sciences 2008
Self-association of human PCSK9 correlates with its LDLR-degrading activity
D Fan, PG Yancey, S Qiu, L Ding, EJ Weeber, MR Linton, S Fazio
Biochemistry 2008
PCSK9 function and physiology
Peterson AS, Fong LG, Young SG
Journal of lipid research 2008
The proprotein convertases are potential targets in the treatment of dyslipidemia
NG Seidah, A Prat
Journal of Molecular Medicine 2007
Molecular biology of PCSK9: its role in LDL metabolism
JD Horton, JC Cohen, HH Hobbs
Trends in Biochemical Sciences 2007
Proprotein convertase subtilisin/kexin type 9 (PCSK9) gene is a risk factor of large-vessel atherosclerosis stroke
S Abboud, PJ Karhunen, D Lütjohann, S Goebeler, T Luoto, S Friedrichs, T Lehtimaki, M Pandolfo, R Laaksonen
PloS one 2007
Versatility in ligand recognition by LDL receptor family proteins: advances and frontiers
SC Blacklow
Current Opinion in Structural Biology 2007
The self-inhibited structure of full-length PCSK9 at 1.9 A reveals structural homology with resistin within the C-terminal domain
EN Hampton, MW Knuth, J Li, JL Harris, SA Lesley, G Spraggon
Proceedings of the National Academy of Sciences 2007
Secreted PCSK9 promotes LDL receptor degradation independently of proteolytic activity
J Li, C Tumanut, JA Gavigan, WJ Huang, EN Hampton, R Tumanut, KF Suen, JW Trauger, G Spraggon, SA Lesley, G Liau, D Yowe, JL Harris
Biochemical Journal 2007
Degradation of the LDL receptors by PCSK9 is not mediated by a secreted protein acted upon by PCSK9 extracellularly
ØL Holla, J Cameron, KE Berge, T Ranheim, TP Leren
BMC cell biology 2007
The Metalloprotease Inhibitor TIMP-3 Regulates Amyloid Precursor Protein and Apolipoprotein E Receptor Proteolysis
HS Hoe, MJ Cooper, MP Burns, PA Lewis, M van der Brug, G Chakraborty, CM Cartagena, DT Pak, MR Cookson, GW Rebeck
The Journal of neuroscience : the official journal of the Society for Neuroscience 2007

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