CoChat
Sign Up
Cited by 150

The DOI matches its Crossref record; 32 of the 32 references it cites were found in a registry or an index.

Targeting PCSK9 to tackle cardiovascular disease

Hummelgaard, Sandra, Vilstrup, Joachim Pold, Gustafsen, Camilla, Glerup, Simon, Weyer, Kathrin·2023·Pharmacology & Therapeutics
DOI 10.1016/j.pharmthera.2023.108480
Open this paper in CoChat — free account

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1016/j.pharmthera.2023.108480

Cites

32 of 32 references verified0 citation errors · 0 not checkable

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • PCSK9 secreted by the liver binds LDLR, promoting LDLR lysosomal degradation and preventing its recycling back to the cell surface.

    “Proprotein convertase subtilisin/kexin type 9 (PCSK9), secreted by the liver, functions as a competitive binder to low-density lipoprotein receptor (LDLR), promoting LDLR lysosomal degradation and preventing its recycling back to the cell surface.”

    From ABCC4 impairs the clearance of plasma LDL cholesterol through suppressing LDLR expression in the liver (2025) · cites this paper as [9]

    The Figure 3 caption says liver hepatocytes secrete PCSK9, and section 3.2 says PCSK9 binds LDLR, prevents its recycling, and directs the complex to lysosomal degradation. The citing sentence’s additional description of PCSK9 as a “competitive binder” is not established by these passages; sections 3.1 and 3.2 describe different LDLR binding domains for LDL-C and PCSK9. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • PCSK9 inhibitors prevent the degradation of LDLR in hepatocytes.

    “The development of PCSK9 inhibitors (PCSK9i) has manifested their pivotal roles in lipid-lowing therapies by preventing the degradation of LDLR in hepatocytes9,10.”

    From ABCC4 impairs the clearance of plasma LDL cholesterol through suppressing LDLR expression in the liver (2025) · cites this paper as [9]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Flagged first, then by citations

Research works printed but not linked: 194

  1. Abifadel, 2012, Identification and characterization of new gain-of-function mutations in the PCSK9 gene responsible for autosomal dominant hypercholesterolemia, Atherosclerosis, 223, 394, 10.1016/j.atherosclerosis.2012.04.006 · DOI
  2. Abifadel, 2003, Mutations in PCSK9 cause autosomal dominant hypercholesterolemia, Nature Genetics, 34, 154, 10.1038/ng1161 · DOI · Paper page
  3. Ahamad, 2022, Development of small-molecule PCSK9 inhibitors for the treatment of hypercholesterolemia, Drug Discovery Today, 27, 1332, 10.1016/j.drudis.2022.01.014 · DOI
  4. Ahmed, 2013, The genetic spectrum of familial hypercholesterolemia in Pakistan, Clinica Chimica Acta, 421, 219, 10.1016/j.cca.2013.03.017 · DOI
  5. Ai, 2012, Regulation of hepatic LDL receptors by mTORC1 and PCSK9 in mice, The Journal of Clinical Investigation, 122, 1262, 10.1172/JCI61919 · DOI
  6. Allard, 2005, Novel mutations of the PCSK9 gene cause variable phenotype of autosomal dominant hypercholesterolemia, Human Mutation, 26, 497, 10.1002/humu.9383 · DOI
  7. Alleyne, 2020, Series of novel and highly potent cyclic peptide PCSK9 inhibitors derived from an mRNA display screen and optimized via structure-based design, Journal of Medicinal Chemistry, 63, 13796, 10.1021/acs.jmedchem.0c01084 · DOI
  8. Alves, 2015, Characterization of the first PCSK9 gain of function homozygote, Journal of the American College of Cardiology, 66, 2152, 10.1016/j.jacc.2015.08.871 · DOI
  9. Anderson, 1982, Surface distribution and recycling of the low density lipoprotein receptor as visualized with antireceptor antibodies, The Journal of Cell Biology, 93, 523, 10.1083/jcb.93.3.523 · DOI
  10. Anderson, 1977, Role of the coated endocytic vesicle in the uptake of receptor-bound low density lipoprotein in human fibroblasts, Cell, 10, 351, 10.1016/0092-8674(77)90022-8 · DOI · Paper page
  11. Atreya, 2020, Proprotein convertase Subtilisin/Kexin type 9 loss-of-function is detrimental to the juvenile host with septic shock, Critical Care Medicine, 48, 1513, 10.1097/CCM.0000000000004487 · DOI
  12. Badimon, 2021, PCSK9 and LRP5 in macrophage lipid internalization and inflammation, Cardiovascular Research, 117, 2054, 10.1093/cvr/cvaa254 · DOI
  13. Bagdanoff, 2023, Clearance of plasma PCSK9 via the asialoglycoprotein receptor mediated by heterobifunctional ligands, Cell Chemical Biology, 30, 97, 10.1016/j.chembiol.2022.12.003 · DOI
  14. Barale, 2020, Platelet function and activation markers in primary hypercholesterolemia treated with anti-PCSK9 monoclonal antibody: A 12-month follow-up, Nutrition, Metabolism, and Cardiovascular Diseases, 30, 282, 10.1016/j.numecd.2019.09.012 · DOI
  15. Ben Djoudi Ouadda, 2019, Ser-phosphorylation of PCSK9 (Proprotein convertase Subtilisin-Kexin 9) by Fam20C (family with sequence similarity 20, member C) kinase enhances its ability to degrade the LDLR (low-density lipoprotein receptor), Arteriosclerosis, Thrombosis, and Vascular Biology, 39, 1996, 10.1161/ATVBAHA.119.313247 · DOI · Paper page
  16. Benjannet, 2004, NARC-1/PCSK9 and its natural mutants: Zymogen cleavage and effects on the low density lipoprotein (LDL) receptor and LDL cholesterol, The Journal of Biological Chemistry, 279, 48865, 10.1074/jbc.M409699200 · DOI · Paper page
  17. Benjannet, 2006, The proprotein convertase (PC) PCSK9 is inactivated by furin and/or PC5/6A: Functional consequences of natural mutations and post-translational modifications, The Journal of Biological Chemistry, 281, 30561, 10.1074/jbc.M606495200 · DOI · Paper page
  18. Benjannet, 2010, Effects of the prosegment and pH on the activity of PCSK9: Evidence for additional processing events, The Journal of Biological Chemistry, 285, 40965, 10.1074/jbc.M110.154815 · DOI
  19. Berge, 2006, Missense mutations in the PCSK9 gene are associated with hypocholesterolemia and possibly increased response to statin therapy, Arteriosclerosis, Thrombosis, and Vascular Biology, 26, 1094, 10.1161/01.ATV.0000204337.81286.1c · DOI · Paper page
  20. Bottomley, 2009, Structural and biochemical characterization of the wild type PCSK9-EGF(AB) complex and natural familial hypercholesterolemia mutants, The Journal of Biological Chemistry, 284, 1313, 10.1074/jbc.M808363200 · DOI
  21. Bourbon, 2008, Familial hypercholesterolaemia in Portugal, Atherosclerosis, 196, 633, 10.1016/j.atherosclerosis.2007.07.019 · DOI
  22. Boyd, 2016, Increased plasma PCSK9 levels are associated with reduced endotoxin clearance and the development of acute organ failures during sepsis, Journal of Innate Immunity, 8, 211, 10.1159/000442976 · DOI
  23. Brousseau, 2022, Identification of a PCSK9-LDLR disruptor peptide with in vivo function, Cell Chemical Biology, 29, 249, 10.1016/j.chembiol.2021.08.012 · DOI
  24. Brown, 1983, Recycling receptors: The round-trip itinerary of migrant membrane proteins, Cell, 32, 663, 10.1016/0092-8674(83)90052-1 · DOI · Paper page
  25. von Brühl, 2012, Monocytes, neutrophils, and platelets cooperate to initiate and propagate venous thrombosis in mice in vivo, The Journal of Experimental Medicine, 209, 819, 10.1084/jem.20112322 · DOI
  26. Burdick, 2020, Design of organo-peptides as bipartite PCSK9 antagonists, ACS Chemical Biology, 15, 425, 10.1021/acschembio.9b00899 · DOI
  27. Camera, 2018, PCSK9 as a positive modulator of platelet activation, Journal of the American College of Cardiology, 71, 952, 10.1016/j.jacc.2017.11.069 · DOI
  28. Cameron, 2009, Mutation S462P in the PCSK9 gene reduces secretion of mutant PCSK9 without affecting the autocatalytic cleavage, Atherosclerosis, 203, 161, 10.1016/j.atherosclerosis.2008.10.007 · DOI
  29. Cameron, 2006, Effect of mutations in the PCSK9 gene on the cell surface LDL receptors, Human Molecular Genetics, 15, 1551, 10.1093/hmg/ddl077 · DOI · Paper page
  30. Cameron, 2008, Characterization of novel mutations in the catalytic domain of the PCSK9 gene, Journal of Internal Medicine, 263, 420, 10.1111/j.1365-2796.2007.01915.x · DOI
  31. Cariou, 2009, PCSK9 dominant negative mutant results in increased LDL catabolic rate and familial hypobetalipoproteinemia, Arteriosclerosis, Thrombosis, and Vascular Biology, 29, 2191, 10.1161/ATVBAHA.109.194191 · DOI
  32. Chan, 2009, A proprotein convertase subtilisin/kexin type 9 neutralizing antibody reduces serum cholesterol in mice and nonhuman primates, Proceedings of the National Academy of Sciences of the United States of America, 106, 9820, 10.1073/pnas.0903849106 · DOI · Paper page
  33. Chen, 2005, A common PCSK9 haplotype, encompassing the E670G coding single nucleotide polymorphism, is a novel genetic marker for plasma low-density lipoprotein cholesterol levels and severity of coronary atherosclerosis, Journal of the American College of Cardiology, 45, 1611, 10.1016/j.jacc.2005.01.051 · DOI
  34. Chen, 2013, SEC24A deficiency lowers plasma cholesterol through reduced PCSK9 secretion, Elife, 2, 10.7554/eLife.00444 · DOI · Paper page
  35. Chen, 2014, PCSK9 is present in human cerebrospinal fluid and is maintained at remarkably constant concentrations throughout the course of the day, Lipids, 49, 445, 10.1007/s11745-014-3895-6 · DOI · Paper page
  36. Cohen, 2013, Genetics. Simple genetics for a complex disease, Science, 340, 689, 10.1126/science.1239101 · DOI
  37. Costet, 2006, Hepatic PCSK9 expression is regulated by nutritional status via insulin and sterol regulatory element-binding protein 1c, The Journal of Biological Chemistry, 281, 6211, 10.1074/jbc.M508582200 · DOI
  38. Courtemanche, 2018, PCSK9 concentrations in cerebrospinal fluid are not specifically increased in Alzheimer’s disease, Journal of Alzheimer’s Disease, 62, 1519, 10.3233/JAD-170993 · DOI · Paper page
  39. Cunningham, 2007, Structural and biophysical studies of PCSK9 and its mutants linked to familial hypercholesterolemia, Nature Structural & Molecular Biology, 14, 413, 10.1038/nsmb1235 · DOI · Paper page
  40. Demers, 2015, PCSK9 induces CD36 degradation and affects long-chain fatty acid uptake and triglyceride metabolism in adipocytes and in mouse liver, Arteriosclerosis, Thrombosis, and Vascular Biology, 35, 2517, 10.1161/ATVBAHA.115.306032 · DOI · Paper page
  41. DeVay, 2013, Characterization of proprotein convertase subtilisin/kexin type 9 (PCSK9) trafficking reveals a novel lysosomal targeting mechanism via amyloid precursor-like protein 2 (APLP2), The Journal of Biological Chemistry, 288, 10805, 10.1074/jbc.M113.453373 · DOI · Paper page
  42. Di Filippo, 2017, A case of hypocholesterolemia and steatosis in a carrier of a PCSK9 loss-of-function mutation and polymorphisms predisposing to nonalcoholic fatty liver disease, Journal of Clinical Lipidology, 11, 1101, 10.1016/j.jacl.2017.06.005 · DOI
  43. Di Taranto, 2017, Identification and in vitro characterization of two new PCSK9 gain of function variants found in patients with familial hypercholesterolemia, Scientific Reports, 7, 15282, 10.1038/s41598-017-15543-x · DOI
  44. Ding, 2018, PCSK9 regulates expression of scavenger receptors and ox-LDL uptake in macrophages, Cardiovascular Research, 114, 1145, 10.1093/cvr/cvy079 · DOI · Paper page
  45. Ding, 2020, NLRP3 inflammasome via IL-1β regulates PCSK9 secretion, Theranostics, 10, 7100, 10.7150/thno.45939 · DOI
  46. Dong, 2010, Strong induction of PCSK9 gene expression through HNF1alpha and SREBP2: Mechanism for the resistance to LDL-cholesterol lowering effect of statins in dyslipidemic hamsters, Journal of Lipid Research, 51, 1486, 10.1194/jlr.M003566 · DOI
  47. Dubuc, 2004, Statins upregulate PCSK9, the gene encoding the proprotein convertase neural apoptosis-regulated convertase-1 implicated in familial hypercholesterolemia, Arteriosclerosis, Thrombosis, and Vascular Biology, 24, 1454, 10.1161/01.ATV.0000134621.14315.43 · DOI · Paper page
  48. Dubuc, 2010, A new method for measurement of total plasma PCSK9: Clinical applications, Journal of Lipid Research, 51, 140, 10.1194/jlr.M900273-JLR200 · DOI
  49. Dwivedi, 2016, Differential expression of PCSK9 modulates infection, inflammation, and coagulation in a murine model of sepsis, Shock, 46, 672, 10.1097/SHK.0000000000000682 · DOI
  50. Essalmani, 2011, In vivo evidence that furin from hepatocytes inactivates PCSK9, The Journal of Biological Chemistry, 286, 4257, 10.1074/jbc.M110.192104 · DOI · Paper page
  51. Fasano, 2007, A novel loss of function mutation of PCSK9 gene in white subjects with low-plasma low-density lipoprotein cholesterol, Arteriosclerosis, Thrombosis, and Vascular Biology, 27, 677, 10.1161/01.ATV.0000255311.26383.2f · DOI
  52. Feng, 2019, A genetic approach to the association between PCSK9 and sepsis, JAMA Network Open, 2, 10.1001/jamanetworkopen.2019.11130 · DOI
  53. Ference, 2017, Low-density lipoproteins cause atherosclerotic cardiovascular disease. 1. Evidence from genetic, epidemiologic, and clinical studies. A consensus statement from the European atherosclerosis society consensus panel, European Heart Journal, 38, 2459, 10.1093/eurheartj/ehx144 · DOI · Paper page
  54. Fisher, 2007, Effects of pH and low density lipoprotein (LDL) on PCSK9-dependent LDL receptor regulation, The Journal of Biological Chemistry, 282, 20502, 10.1074/jbc.M701634200 · DOI · Paper page
  55. Fu, 2017, APP, APLP2 and LRP1 interact with PCSK9 but are not required for PCSK9-mediated degradation of the LDLR in vivo, Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids, 1862, 883, 10.1016/j.bbalip.2017.05.002 · DOI · Paper page
  56. Fuchs, 2010, Extracellular DNA traps promote thrombosis, Proceedings of the National Academy of Sciences of the United States of America, 107, 15880, 10.1073/pnas.1005743107 · DOI
  57. Gallagher, 1995, The prosegment-subtilisin BPN’ complex: Crystal structure of a specific ’foldase, Structure, 3, 907, 10.1016/S0969-2126(01)00225-8 · DOI
  58. Galvan, 2019, Cell-associated heparin-like molecules modulate the ability of LDL to regulate PCSK9 uptake, Journal of Lipid Research, 60, 71, 10.1194/jlr.M087189 · DOI
  59. Gencer, 2020, Efficacy and safety of lowering LDL cholesterol in older patients: A systematic review and meta-analysis of randomised controlled trials, Lancet, 396, 1637, 10.1016/S0140-6736(20)32332-1 · DOI · Paper page
  60. Genga, 2018, Impact of PCSK9 loss-of-function genotype on 1-year mortality and recurrent infection in sepsis survivors, EBioMedicine, 38, 257, 10.1016/j.ebiom.2018.11.032 · DOI
  61. Geschwindner, 2015, Characterisation of de novo mutations in the C-terminal domain of proprotein convertase subtilisin/kexin type 9, Protein Engineering, Design & Selection, 28, 117, 10.1093/protein/gzv008 · DOI
  62. Giugliano, 2017, Clinical efficacy and safety of achieving very low LDL-cholesterol concentrations with the PCSK9 inhibitor evolocumab: A prespecified secondary analysis of the FOURIER trial, Lancet, 390, 1962, 10.1016/S0140-6736(17)32290-0 · DOI · Paper page
  63. Giunzioni, 2016, Local effects of human PCSK9 on the atherosclerotic lesion, The Journal of Pathology, 238, 52, 10.1002/path.4630 · DOI
  64. Gustafsen, 2017, Heparan sulfate proteoglycans present PCSK9 to the LDL receptor, Nature Communications, 8, 503, 10.1038/s41467-017-00568-7 · DOI
  65. Gutiérrez-Cirlos, 2011, Familial hypobetalipoproteinemia in a hospital survey: Genetics, metabolism and non-alcoholic fatty liver disease, Annals of Hepatology, 10, 155, 10.1016/S1665-2681(19)31564-9 · DOI
  66. Haas, 2016, The role of Proprotein convertase Subtilisin/Kexin type 9 in nephrotic syndrome-associated hypercholesterolemia, Circulation, 134, 61, 10.1161/CIRCULATIONAHA.115.020912 · DOI
  67. Hallman, 2007, Relation of PCSK9 mutations to serum low-density lipoprotein cholesterol in childhood and adulthood (from the Bogalusa heart study), The American Journal of Cardiology, 100, 69, 10.1016/j.amjcard.2007.02.057 · DOI
  68. Hampton, 2007, The self-inhibited structure of full-length PCSK9 at 1.9 A reveals structural homology with resistin within the C-terminal domain, Proceedings of the National Academy of Sciences of the United States of America, 104, 14604, 10.1073/pnas.0703402104 · DOI
  69. Han, 2015, Genetic testing of Korean familial hypercholesterolemia using whole-exome sequencing, PLoS One, 10
  70. Hay, 2022, Genetic analysis of the PCSK9 locus in psychological, psychiatric, metabolic and cardiovascular traits in UK Biobank, European Journal of Human Genetics, 30, 1380, 10.1038/s41431-022-01107-9 · DOI · Paper page
  71. Holla Ø, 2011, Removal of acidic residues of the prodomain of PCSK9 increases its activity towards the LDL receptor, Biochemical and Biophysical Research Communications, 406, 234, 10.1016/j.bbrc.2011.02.023 · DOI
  72. Homer, 2008, Identification and characterization of two non-secreted PCSK9 mutants associated with familial hypercholesterolemia in cohorts from New Zealand and South Africa, Atherosclerosis, 196, 659, 10.1016/j.atherosclerosis.2007.07.022 · DOI · Paper page
  73. Hooper, 2013, Anti-PCSK9 therapies for the treatment of hypercholesterolemia, Expert Opinion on Biological Therapy, 13, 429, 10.1517/14712598.2012.748743 · DOI
  74. Hooper, 2007, The C679X mutation in PCSK9 is present and lowers blood cholesterol in a Southern African population, Atherosclerosis, 193, 445, 10.1016/j.atherosclerosis.2006.08.039 · DOI
  75. Hopkins, 2015, Characterization of autosomal dominant hypercholesterolemia caused by PCSK9 gain of function mutations and its specific treatment with alirocumab, a PCSK9 monoclonal antibody, Circulation. Cardiovascular Genetics, 8, 823, 10.1161/CIRCGENETICS.115.001129 · DOI
  76. Horton, 2009, PCSK9: A convertase that coordinates LDL catabolism, Journal of Lipid Research, 50, S172, 10.1194/jlr.R800091-JLR200 · DOI · Paper page
  77. Horton, 2003, Combined analysis of oligonucleotide microarray data from transgenic and knockout mice identifies direct SREBP target genes, Proceedings of the National Academy of Sciences of the United States of America, 100, 12027, 10.1073/pnas.1534923100 · DOI · Paper page
  78. Hossain, 2015, Lipopolysaccharide augments the uptake of oxidized LDL by up-regulating lectin-like oxidized LDL receptor-1 in macrophages, Molecular and Cellular Biochemistry, 400, 29, 10.1007/s11010-014-2259-0 · DOI
  79. Hu, 2017, Increased sortilin and its independent effect on circulating proprotein convertase subtilisin/kexin type 9 (PCSK9) in statin-naive patients with coronary artery disease, International Journal of Cardiology, 227, 61, 10.1016/j.ijcard.2016.11.064 · DOI
  80. Huijgen, 2012, Genetic variation in APOB, PCSK9, and ANGPTL3 in carriers of pathogenic autosomal dominant hypercholesterolemic mutations with unexpected low LDL-Cl Levels, Human Mutation, 33, 448, 10.1002/humu.21660 · DOI
  81. Hunt, 2000, Genetic localization to chromosome 1p32 of the third locus for familial hypercholesterolemia in a Utah kindred, Arteriosclerosis, Thrombosis, and Vascular Biology, 20, 1089, 10.1161/01.ATV.20.4.1089 · DOI
  82. Jeong, 2008, Sterol-dependent regulation of proprotein convertase subtilisin/kexin type 9 expression by sterol-regulatory element binding protein-2, Journal of Lipid Research, 49, 399, 10.1194/jlr.M700443-JLR200 · DOI · Paper page
  83. Jia, 2022, Sex difference in circulating PCSK9 and its clinical implications, Frontiers in Pharmacology, 13, 10.3389/fphar.2022.953845 · DOI
  84. Jin, 2014, Plasma PCSK9 in nephrotic syndrome and in peritoneal dialysis: A cross-sectional study, American Journal of Kidney Diseases, 63, 584, 10.1053/j.ajkd.2013.10.042 · DOI
  85. Johns, 2023, Orally bioavailable macrocyclic peptide that inhibits binding of PCSK9 to the low density lipoprotein receptor, Circulation., 10.1161/CIRCULATIONAHA.122.063372 · DOI
  86. Kastelein, 2016, Safety and efficacy of LY3015014, a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 (PCSK9): A randomized, placebo-controlled phase 2 study, European Heart Journal, 37, 1360, 10.1093/eurheartj/ehv707 · DOI
  87. Khera, 2016, Diagnostic yield and clinical utility of sequencing familial hypercholesterolemia genes in patients with severe hypercholesterolemia, Journal of the American College of Cardiology, 67, 2578, 10.1016/j.jacc.2016.03.520 · DOI · Paper page
  88. Khvorova, 2017, Oligonucleotide therapeutics - A new class of cholesterol-lowering drugs, The New England Journal of Medicine, 376, 4, 10.1056/NEJMp1614154 · DOI
  89. Kotowski, 2006, A spectrum of PCSK9 alleles contributes to plasma levels of low-density lipoprotein cholesterol, American Journal of Human Genetics, 78, 410, 10.1086/500615 · DOI · Paper page
  90. Krysa, 2017, Nutritional and lipid modulation of PCSK9: Effects on cardiometabolic risk factors, The Journal of Nutrition, 147, 473, 10.3945/jn.116.235069 · DOI
  91. Kwakernaak, 2013, Proprotein convertase subtilisin-kexin type 9 is elevated in proteinuric subjects: Relationship with lipoprotein response to antiproteinuric treatment, Atherosclerosis, 226, 459, 10.1016/j.atherosclerosis.2012.11.009 · DOI
  92. Kwon, 2008, Molecular basis for LDL receptor recognition by PCSK9, Proceedings of the National Academy of Sciences of the United States of America, 105, 1820, 10.1073/pnas.0712064105 · DOI · Paper page
  93. Lagace, 2006, Secreted PCSK9 decreases the number of LDL receptors in hepatocytes and in livers of parabiotic mice, The Journal of Clinical Investigation, 116, 2995, 10.1172/JCI29383 · DOI · Paper page
  94. Lakoski, 2009, Genetic and metabolic determinants of plasma PCSK9 levels, The Journal of Clinical Endocrinology and Metabolism, 94, 2537, 10.1210/jc.2009-0141 · DOI · Paper page
  95. Landlinger, 2017, The AT04A vaccine against proprotein convertase subtilisin/kexin type 9 reduces total cholesterol, vascular inflammation, and atherosclerosis in APOE*3Leiden.CETP mice, European Heart Journal, 38, 2499, 10.1093/eurheartj/ehx260 · DOI
  96. Lange, 2014, Whole-exome sequencing identifies rare and low-frequency coding variants associated with LDL cholesterol, American Journal of Human Genetics, 94, 233, 10.1016/j.ajhg.2014.01.010 · DOI
  97. Langsted, 2016, PCSK9 R46L loss-of-function mutation reduces lipoprotein(a), LDL cholesterol, and risk of aortic valve stenosis, The Journal of Clinical Endocrinology and Metabolism, 101, 3281, 10.1210/jc.2016-1206 · DOI · Paper page
  98. Leander, 2016, Circulating Proprotein convertase Subtilisin/Kexin type 9 (PCSK9) predicts future risk of cardiovascular events independently of established risk factors, Circulation, 133, 1230, 10.1161/CIRCULATIONAHA.115.018531 · DOI
  99. Lee, 2017, Rare and common variants of APOB and PCSK9 in Korean patients with extremely low low-density lipoprotein-cholesterol levels, PLoS One, 12
  100. Leren, 2004, Mutations in the PCSK9 gene in Norwegian subjects with autosomal dominant hypercholesterolemia, Clinical Genetics, 65, 419, 10.1111/j.0009-9163.2004.0238.x · DOI
  101. Leung, 2019, Reduced Proprotein convertase subtilisin/kexin 9 (PCSK9) function increases lipoteichoic acid clearance and improves outcomes in gram positive septic shock patients, Scientific Reports, 9, 10588, 10.1038/s41598-019-46745-0 · DOI
  102. Li, 2009, Hepatocyte nuclear factor 1alpha plays a critical role in PCSK9 gene transcription and regulation by the natural hypocholesterolemic compound berberine, The Journal of Biological Chemistry, 284, 28885, 10.1074/jbc.M109.052407 · DOI
  103. Li, 2007, Secreted PCSK9 promotes LDL receptor degradation independently of proteolytic activity, The Biochemical Journal, 406, 203, 10.1042/BJ20070664 · DOI
  104. Li, 2017, Familial hypercholesterolemia phenotype in Chinese patients undergoing coronary angiography, Arteriosclerosis, Thrombosis, and Vascular Biology, 37, 570, 10.1161/ATVBAHA.116.308456 · DOI
  105. Lin, 2010, A novel mutation in proprotein convertase subtilisin/kexin type 9 gene leads to familial hypercholesterolemia in a Chinese family, Chinese Medical Journal, 123, 1133
  106. Lipari, 2012, Furin-cleaved proprotein convertase subtilisin/kexin type 9 (PCSK9) is active and modulates low density lipoprotein receptor and serum cholesterol levels, The Journal of Biological Chemistry, 287, 43482, 10.1074/jbc.M112.380618 · DOI
  107. Lo Surdo, 2011, Mechanistic implications for LDL receptor degradation from the PCSK9/LDLR structure at neutral pH, EMBO Reports, 12, 1300, 10.1038/embor.2011.205 · DOI · Paper page
  108. Luquero, 2021, PCSK9 functions in atherosclerosis are not limited to plasmatic LDL-cholesterol regulation, Frontiers in Cardiovascular Medicine, 8, 10.3389/fcvm.2021.639727 · DOI
  109. Macchi, 2020, Depression and cardiovascular risk-association among Beck depression inventory, PCSK9 levels and insulin resistance, Cardiovascular Diabetology, 19, 187, 10.1186/s12933-020-01158-6 · DOI · Paper page
  110. Mach, 2020, 2019 ESC/EAS guidelines for the management of dyslipidaemias: Lipid modification to reduce cardiovascular risk, European Heart Journal, 41, 111, 10.1093/eurheartj/ehz455 · DOI · Paper page
  111. Mannarino, 2018, PCSK9 and neurocognitive function: Should it be still an issue after FOURIER and EBBINGHAUS results?, Journal of Clinical Lipidology, 12, 1123, 10.1016/j.jacl.2018.05.012 · DOI
  112. Marku, 2022, Pancreatic PCSK9 controls the organization of the β-cell secretory pathway via LDLR-cholesterol axis, Metabolism, 136, 10.1016/j.metabol.2022.155291 · DOI
  113. Marmontel, 2018, Single, short in-del, and copy number variations detection in monogenic dyslipidemia using a next-generation sequencing strategy, Clinical Genetics, 94, 132, 10.1111/cge.13250 · DOI
  114. Martínez-Oliván, 2014, LDL receptor/lipoprotein recognition: Endosomal weakening of ApoB and ApoE binding to the convex face of the LR5 repeat, The FEBS Journal, 281, 1534, 10.1111/febs.12721 · DOI
  115. Maxwell, 2004, Adenoviral-mediated expression of Pcsk9 in mice results in a low-density lipoprotein receptor knockout phenotype, Proceedings of the National Academy of Sciences of the United States of America, 101, 7100, 10.1073/pnas.0402133101 · DOI · Paper page
  116. Mayer, 2008, Annexin A2 is a C-terminal PCSK9-binding protein that regulates endogenous low density lipoprotein receptor levels, The Journal of Biological Chemistry, 283, 31791, 10.1074/jbc.M805971200 · DOI · Paper page
  117. Mayne, 2011, Novel loss-of-function PCSK9 variant is associated with low plasma LDL cholesterol in a French-Canadian family and with impaired processing and secretion in cell culture, Clinical Chemistry, 57, 1415, 10.1373/clinchem.2011.165191 · DOI · Paper page
  118. Mayne, 2013, Differential effects of PCSK9 loss of function variants on serum lipid and PCSK9 levels in Caucasian and African Canadian populations, Lipids in Health and Disease, 12, 70, 10.1186/1476-511X-12-70 · DOI
  119. McKenney, 2012, Safety and efficacy of a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 serine protease, SAR236553/REGN727, in patients with primary hypercholesterolemia receiving ongoing stable atorvastatin therapy, Journal of the American College of Cardiology, 59, 2344, 10.1016/j.jacc.2012.03.007 · DOI
  120. Mikaeeli, 2020, Functional analysis of natural PCSK9 mutants in modern and archaic humans, The FEBS Journal, 287, 515, 10.1111/febs.15036 · DOI
  121. Miyake, 2008, Genetic variants in PCSK9 in the Japanese population: Rare genetic variants in PCSK9 might collectively contribute to plasma LDL cholesterol levels in the general population, Atherosclerosis, 196, 29, 10.1016/j.atherosclerosis.2006.12.035 · DOI
  122. Molina-Jijon, 2020, Secretion of the epithelial sodium channel chaperone PCSK9 from the cortical collecting duct links sodium retention with hypercholesterolemia in nephrotic syndrome, Kidney International, 98, 1449, 10.1016/j.kint.2020.06.045 · DOI
  123. Momtazi-Borojeni, 2021, PCSK9 immunization using nanoliposomes: Preventive efficacy against hypercholesterolemia and atherosclerosis, Archives of Medical Science, 17, 1365, 10.5114/aoms/133885 · DOI
  124. Nabel, 2012, A tale of coronary artery disease and myocardial infarction, The New England Journal of Medicine, 366, 54, 10.1056/NEJMra1112570 · DOI
  125. Navarese, 2015, Effects of proprotein convertase Subtilisin/Kexin type 9 antibodies in adults with hypercholesterolemia: A systematic review and meta-analysis, Annals of Internal Medicine, 163, 40, 10.7326/M14-2957 · DOI
  126. Navarese, 2017, Association of PCSK9 with platelet reactivity in patients with acute coronary syndrome treated with prasugrel or ticagrelor: The PCSK9-REACT study, International Journal of Cardiology, 227, 644, 10.1016/j.ijcard.2016.10.084 · DOI
  127. Ni, 2011, A PCSK9-binding antibody that structurally mimics the EGF(A) domain of LDL-receptor reduces LDL cholesterol in vivo, Journal of Lipid Research, 52, 78, 10.1194/jlr.M011445 · DOI
  128. Noguchi, 2010, The E32K variant of PCSK9 exacerbates the phenotype of familial hypercholesterolaemia by increasing PCSK9 function and concentration in the circulation, Atherosclerosis, 210, 166, 10.1016/j.atherosclerosis.2009.11.018 · DOI
  129. Norsworthy, 2014, Targeted genetic testing for familial hypercholesterolaemia using next generation sequencing: A population-based study, BMC Medical Genetics, 15, 70, 10.1186/1471-2350-15-70 · DOI
  130. Nowak, 2018, A Mendelian randomization study of the effects of blood lipids on breast cancer risk, Nature Communications, 9, 3957, 10.1038/s41467-018-06467-9 · DOI
  131. Nozue, 2016, Effects of statin therapy on plasma proprotein convertase Subtilisin/kexin type 9 and sortilin levels in statin-naive patients with coronary artery disease, Journal of Atherosclerosis and Thrombosis, 23, 848, 10.5551/jat.33407 · DOI
  132. Persson, 2010, Circulating proprotein convertase subtilisin kexin type 9 has a diurnal rhythm synchronous with cholesterol synthesis and is reduced by fasting in humans, Arteriosclerosis, Thrombosis, and Vascular Biology, 30, 2666, 10.1161/ATVBAHA.110.214130 · DOI · Paper page
  133. Peyot, 2021, Substantial PCSK9 inactivation in β-cells does not modify glucose homeostasis or insulin secretion in mice, Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids, 1866
  134. Piper, 2007, The crystal structure of PCSK9: A regulator of plasma LDL-cholesterol, Structure, 15, 545, 10.1016/j.str.2007.04.004 · DOI · Paper page
  135. Pisciotta, 2006, Additive effect of mutations in LDLR and PCSK9 genes on the phenotype of familial hypercholesterolemia, Atherosclerosis, 186, 433, 10.1016/j.atherosclerosis.2005.08.015 · DOI
  136. Poirier, 2006, Implication of the proprotein convertase NARC-1/PCSK9 in the development of the nervous system, Journal of Neurochemistry, 98, 838, 10.1111/j.1471-4159.2006.03928.x · DOI · Paper page
  137. Portal, 2023, vol. 2023
  138. Qamar, 2019, Interindividual variation in low-density lipoprotein cholesterol level reduction with evolocumab: An analysis of FOURIER trial data, JAMA Cardiology, 4, 59, 10.1001/jamacardio.2018.4178 · DOI
  139. Raal, 2013, Elevated PCSK9 levels in untreated patients with heterozygous or homozygous familial hypercholesterolemia and the response to high-dose statin therapy, Journal of the American Heart Association, 2, 10.1161/JAHA.112.000028 · DOI
  140. Ramin-Mangata, 2021, Effects of proprotein convertase subtilisin kexin type 9 modulation in human pancreatic beta cells function, Atherosclerosis, 326, 47, 10.1016/j.atherosclerosis.2021.03.044 · DOI
  141. Rannikko, 2019, Reduced plasma PCSK9 response in patients with bacteraemia is associated with mortality, Journal of Internal Medicine, 286, 553, 10.1111/joim.12946 · DOI
  142. Rashid, 2005, Decreased plasma cholesterol and hypersensitivity to statins in mice lacking Pcsk9, Proceedings of the National Academy of Sciences of the United States of America, 102, 5374, 10.1073/pnas.0501652102 · DOI · Paper page
  143. Ridker, 2016, Plasma proprotein convertase subtilisin/kexin type 9 levels and the risk of first cardiovascular events, European Heart Journal, 37, 554, 10.1093/eurheartj/ehv568 · DOI
  144. Robinson, 2015, Efficacy and safety of alirocumab in reducing lipids and cardiovascular events, The New England Journal of Medicine, 372, 1489, 10.1056/NEJMoa1501031 · DOI · Paper page
  145. Rudenko, 2002, Structure of the LDL receptor extracellular domain at endosomal pH, Science, 298, 2353, 10.1126/science.1078124 · DOI · Paper page
  146. Sabatine, 2017, Cardiovascular safety and efficacy of the PCSK9 inhibitor evolocumab in patients with and without diabetes and the effect of evolocumab on glycaemia and risk of new-onset diabetes: A prespecified analysis of the FOURIER randomised controlled trial, The Lancet Diabetes and Endocrinology, 5, 941, 10.1016/S2213-8587(17)30313-3 · DOI · Paper page
  147. Sahebkar, 2015, Effect of statin therapy on plasma proprotein convertase subtilisin kexin 9 (PCSK9) concentrations: A systematic review and meta-analysis of clinical trials, Diabetes, Obesity & Metabolism, 17, 1042, 10.1111/dom.12536 · DOI
  148. Saitoski, 2022, Proprotein convertase PCSK9 affects expression of key surface proteins in human pancreatic beta cells via intracellular and extracellular regulatory circuits, The Journal of Biological Chemistry, 298, 10.1016/j.jbc.2022.102096 · DOI
  149. Sarkar, 2020, A transient amphipathic helix in the prodomain of PCSK9 facilitates binding to low-density lipoprotein particles, The Journal of Biological Chemistry, 295, 2285, 10.1074/jbc.RA119.010221 · DOI
  150. Schroeder, 2015, Proteolytic cleavage of antigen extends the durability of an anti-PCSK9 monoclonal antibody, Journal of Lipid Research, 56, 2124, 10.1194/jlr.M061903 · DOI
  151. Schuster, 2019, Anti-PCSK9 antibodies inhibit pro-atherogenic mechanisms in APOE*3Leiden.CETP mice, Scientific Reports, 9, 11079, 10.1038/s41598-019-47242-0 · DOI
  152. Seidah, 2003, The secretory proprotein convertase neural apoptosis-regulated convertase 1 (NARC-1): Liver regeneration and neuronal differentiation, Proceedings of the National Academy of Sciences of the United States of America, 100, 928, 10.1073/pnas.0335507100 · DOI · Paper page
  153. Seidah, 2012, The biology and therapeutic targeting of the proprotein convertases, Nature Reviews. Drug Discovery, 11, 367, 10.1038/nrd3699 · DOI · Paper page
  154. Seidah, 2022, The multifaceted biology of PCSK9, Endocrine Reviews, 43, 558, 10.1210/endrev/bnab035 · DOI · Paper page
  155. Setia, 2016, Spectrum of mutations in homozygous familial hypercholesterolemia in India, with four novel mutations, Atherosclerosis, 255, 31, 10.1016/j.atherosclerosis.2016.10.028 · DOI
  156. Shapiro, 2018, Pcsk9, Circulation Research, 122, 1420, 10.1161/CIRCRESAHA.118.311227 · DOI · Paper page
  157. Shrestha, 2021, Hypercholesterolemia in progressive renal failure is associated with changes in hepatic heparan sulfate - PCSK9 interaction, Journal of the American Society of Nephrology, 32, 1371, 10.1681/ASN.2020091376 · DOI
  158. Slimani, 2012, Effect of mutations in LDLR and PCSK9 genes on phenotypic variability in Tunisian familial hypercholesterolemia patients, Atherosclerosis, 222, 158, 10.1016/j.atherosclerosis.2012.02.018 · DOI
  159. Stein, 2012, Lancet, 380, 29, 10.1016/S0140-6736(12)60771-5 · DOI
  160. Stenson, 2014, The human gene mutation database: Building a comprehensive mutation repository for clinical and molecular genetics, diagnostic testing and personalized genomic medicine, Human Genetics, 133, 1, 10.1007/s00439-013-1358-4 · DOI
  161. Südhof, 1985, The LDL receptor gene: A mosaic of exons shared with different proteins, Science, 228, 815, 10.1126/science.2988123 · DOI · Paper page
  162. Sun, 2012, Proprotein convertase subtilisin/kexin type 9 deficiency reduces melanoma metastasis in liver, Neoplasia, 14, 1122, 10.1593/neo.121252 · DOI
  163. Tajima, 2018, Blood lipid-related low-frequency variants in LDLR and PCSK9 are associated with onset age and risk of myocardial infarction in Japanese, Scientific Reports, 8, 8107, 10.1038/s41598-018-26453-x · DOI
  164. Tanaka, 2007, Crystal structure of unautoprocessed precursor of subtilisin from a hyperthermophilic archaeon: Evidence for Ca2+−induced folding, The Journal of Biological Chemistry, 282, 8246, 10.1074/jbc.M610137200 · DOI
  165. Tavori, 2013, Serum proprotein convertase subtilisin/kexin type 9 and cell surface low-density lipoprotein receptor: Evidence for a reciprocal regulation, Circulation, 127, 2403, 10.1161/CIRCULATIONAHA.113.001592 · DOI · Paper page
  166. Taylor, 2016, Statins and their effect on PCSK9-impact and clinical relevance, Current Atherosclerosis Reports, 18, 46, 10.1007/s11883-016-0604-3 · DOI
  167. Timms, 2004, A mutation in PCSK9 causing autosomal-dominant hypercholesterolemia in a Utah pedigree, Human Genetics, 114, 349, 10.1007/s00439-003-1071-9 · DOI
  168. Toth, 2018, Efficacy and safety of lipid lowering by alirocumab in chronic kidney disease, Kidney International, 93, 1397, 10.1016/j.kint.2017.12.011 · DOI
  169. Tsimihodimos, 2011, Dyslipidemia associated with chronic kidney disease, Open Cardiovascular Medicine Journal, 5, 41, 10.2174/1874192401105010041 · DOI
  170. Tucker, 2021, A series of novel, highly potent, and orally bioavailable next-generation tricyclic peptide PCSK9 inhibitors, Journal of Medicinal Chemistry, 64, 16770, 10.1021/acs.jmedchem.1c01599 · DOI
  171. Uhlén, 2015, Proteomics. Tissue-based map of the human proteome, Science, 347, 1260419, 10.1126/science.1260419 · DOI · Paper page
  172. Ultsch, 2019, Identification of a helical segment within the intrinsically disordered region of the PCSK9 prodomain, Journal of Molecular Biology, 431, 885, 10.1016/j.jmb.2018.11.025 · DOI
  173. University of Oxford, T. T. S. G, 2023
  174. Vaca, 2011, Mutational analysis of the LDL receptor and APOB genes in Mexican individuals with autosomal dominant hypercholesterolemia, Atherosclerosis, 218, 391, 10.1016/j.atherosclerosis.2011.06.006 · DOI
  175. Varret, 1999, A third major locus for autosomal dominant hypercholesterolemia maps to 1p34.1-p32, American Journal of Human Genetics, 64, 1378, 10.1086/302370 · DOI
  176. Vecchié, 2021, PCSK9 is associated with mortality in patients with septic shock: Data from the ALBIOS study, Journal of Internal Medicine, 289, 179, 10.1111/joim.13150 · DOI
  177. Verve takes base editors into humans, 2022, Nature Biotechnology, 40, 1159, 10.1038/s41587-022-01445-5 · DOI
  178. Walley, 2014, PCSK9 is a critical regulator of the innate immune response and septic shock outcome, Science Translational Medicine, 6, 258ra143, 10.1126/scitranslmed.3008782 · DOI
  179. Wang, 2017, Proprotein convertase subtilisin/kexin type 9 (PCSK9) deficiency is protective against venous thrombosis in mice, Scientific Reports, 7, 14360, 10.1038/s41598-017-14307-x · DOI
  180. Wang, 2018, Complex genetic architecture in severe hypobetalipoproteinemia, Lipids in Health and Disease, 17, 48, 10.1186/s12944-018-0680-1 · DOI
  181. Wang, 2012, Molecular characterization of proprotein convertase subtilisin/kexin type 9-mediated degradation of the LDLR, Journal of Lipid Research, 53, 1932, 10.1194/jlr.M028563 · DOI · Paper page
  182. Weiner, 2004, Managing dyslipidemia in chronic kidney disease, Journal of General Internal Medicine, 19, 1045, 10.1111/j.1525-1497.2004.40049.x · DOI
  183. Xia, 2021, Regulation of PCSK9 expression and function: Mechanisms and therapeutic implications, Front Cardiovasc Med, 8, 10.3389/fcvm.2021.764038 · DOI · Paper page
  184. Xiang, 2017, The genetic spectrum of familial hypercholesterolemia in the central south region of China, Atherosclerosis, 258, 84, 10.1016/j.atherosclerosis.2017.02.007 · DOI
  185. Xie, 2016, Association between plasma PCSK9 levels and 10-year progression of carotid atherosclerosis beyond LDL-C: A cohort study, International Journal of Cardiology, 215, 293, 10.1016/j.ijcard.2016.04.103 · DOI
  186. Yuan, 2021, Potentiating CD8(+) T cell antitumor activity by inhibiting PCSK9 to promote LDLR-mediated TCR recycling and signaling, Protein & Cell, 12, 240, 10.1007/s13238-021-00821-2 · DOI
  187. Yuan, 2020, PCSK9: A potential therapeutic target for sepsis, Journal of Immunology Research, 2020, 2687692, 10.1155/2020/2687692 · DOI
  188. Zeitlinger, 2021, A phase I study assessing the safety, tolerability, immunogenicity, and low-density lipoprotein cholesterol-lowering activity of immunotherapeutics targeting PCSK9, European Journal of Clinical Pharmacology, 77, 1473, 10.1007/s00228-021-03149-2 · DOI
  189. Zhang, 2008, Structural requirements for PCSK9-mediated degradation of the low-density lipoprotein receptor, Proceedings of the National Academy of Sciences of the United States of America, 105, 13045, 10.1073/pnas.0806312105 · DOI · Paper page
  190. Zhang, 2007, Binding of proprotein convertase subtilisin/kexin type 9 to epidermal growth factor-like repeat A of low density lipoprotein receptor decreases receptor recycling and increases degradation, The Journal of Biological Chemistry, 282, 18602, 10.1074/jbc.M702027200 · DOI · Paper page
  191. Zhang, 2014, Identification of a small peptide that inhibits PCSK9 protein binding to the low density lipoprotein receptor, The Journal of Biological Chemistry, 289, 942, 10.1074/jbc.M113.514067 · DOI
  192. Zhang, 2017, Discovery of a cryptic peptide-binding site on PCSK9 and design of antagonists, Nature Structural & Molecular Biology, 24, 848, 10.1038/nsmb.3453 · DOI
  193. Zhao, 2006, Molecular characterization of loss-of-function mutations in PCSK9 and identification of a compound heterozygote, American Journal of Human Genetics, 79, 514, 10.1086/507488 · DOI
  194. Zhu, 2015, Association of proprotein convertase Subtilisin/Kexin type 9 (PCSK9) with cardiovascular risk in primary prevention, Arteriosclerosis, Thrombosis, and Vascular Biology, 35, 2254, 10.1161/ATVBAHA.115.306172 · DOI

Cited by

Sorted by citations

Metadata

Authors
Hummelgaard, S., Vilstrup, J. P., Gustafsen, C., Glerup, S., & Weyer, K.
Venue
Pharmacology & Therapeutics
Publisher
Elsevier BV
Published
2023-09
Volume
249
Pages
108480
ISSN
0163-7258
DOI
10.1016/j.pharmthera.2023.108480
Cited by
150
References
32
Language
en
Licence

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review