CircuLex Human PCSK9 ELISA Kit

  • Applications
    • ELISA
  • Code # CY-8079
  • Size 96 Assays
  • Price
    $540.75
Specifications

Background

PCSK9 (also known as neural apoptosis-regulated convertase, NARC-1) is a 692-residue extracellular protein expressed primarily in the kidneys, liver and intestines (1) representing the 9th member of the secretory subtilase family. Various genetic observations subsequently mapped PCSK9 as the third gene (along with LDLR and APOB) to cause autosomal dominant hypercholesterolemia (ADH). These studies suggested that gain of function mutations increase plasma levels of LDL-c (2–6), whereas nonsense or missense (loss-of-function) mutations, which interfere with folding or secretion of PCSK9, lead to a reduction of plasma levels of LDL-c and an 88% decrease in the risk of coronary heart disease (CHD) (5). In mice, adenoviral overexpression of PCSK9 results in increased plasma LDL-c level in normal mice but not in LDLR-deficient mice (7). Deletion of PCSK9 causes an increase in level of LDLR protein but not mRNA (8). These findings lead to a hypothesis that PCSK9 exerts its role in cholesterol metabolism through posttranslational down-regulation of LDLR, the receptor responsible for clearing LDL-c from plasma. Evidence is consistent with the secreted form of PCSK9 binding directly to the LDLR and resulting in degradation of the receptor (9, 10). Zhang et al. (11) localized the binding site of PCSK9 in the LDLR to the first epidermal growth factor-like repeat (EGF-A) of the extracellular domain and showed that PCSK9 binding to this site is required for LDLR degradation. In light of these observations and the fact that PCSK9 in the circulation may cause the degradation of hepatic LDLR in the liver, PCSK9 would seem to be an attractive drug target for lowering LDL-c.
  • Application:
    ELISA
  • Components:
    • Microplate
    • 10X Wash Buffer
    • Dilution Buffer
    • Mouse PCSK9 Standard
    • HRP conjugated Detection Antibody
    • Substrate Reagent
    • Stop Solution
  • Description:

    The CircuLex Research Product Human PCSK9 ELISA Kit is used for the quantitative measurement of Human PCSK9 in serum, plasma, cell culture medium and other biological media. It can be used for 96 Assays.

  • Product Type:
    ELISA Kit
  • Research Area:
    Metabolism
  • Short Description:

    CircuLex Human PCSK9 ELISA Kit.

  • Size:
    96 Assays
Citations
  1. Abujrad H et al. Chronic kidney disease on hemodialysis is associated with decreased serum PCSK9 levels. Atherosclerosis. 233, 123-9 (2014),
  2. Bertrand Cariou et al. Association between plasma PCSK9 and gamma-glutamyl transferase levels in diabetic patients. Atherosclerosis. 211: 700-702, 2010,
  3. Blanchard C et al. Roux-en-Y gastric bypass reduces plasma in diet-induced obese mice by affecting trans-intestinal cholesterol excretion and intestinal absorption
  4. Bonde Y et al. Thyroid hormone reduces PCSK9 and stimulates bile acid synthesis in humans. J Lipid Res. 55, 2408-15 (2014),
  5. Butkinaree C et al. Amyloid Precursor-like Protein 2 and Sortilin Do Not Regulate the Convertase-mediated Low Density Lipoprotein Receptor Degradation but Interact with Each Other. J Biol Chem. 290, 18609-20 (2015)
  6. Cameron J et al. Serum levels of proprotein convertase subtilisin/kexin type 9 in subjects with familial hypercholesterolemia indicate that proprotein convertase subtilisin/kexin type 9 is cleared from plasma by low-density lipoprotein receptor_independent pathways. Translational Research. 160, 125-30 (2012)
  7. Cariou B et al. Association between plasma PCSK9 and gamma-glutamyl transferase levels in diabetic patients. Atherosclerosis 211, 700-702 (2010)
  8. Cariou B et al. Clinical aspects of PCSK9. Atherosclerosis. 216: 258-65. 2011,
  9. Cariou B et al. Plasma PCSK9 concentrations during an oral fat load and after short term high-fat, high-fat high-protein and high-fructose diets. Nutr Metab. 10:4. 2013,
  10. Conway V et al. Impact of buttermilk consumption on plasma lipids and surrogate markers of cholesterol homeostasis in men and women. Nutr Metab Cardiovasc Dis. 23, 1255-62 (2013),
  11. Costet P et al. Plasma PCSK9 is increased by Fenofibrate and Atorvastatin in a non additive fashion in diabetic patients. Atherosclerosis 212, 246-251 (2010)
  12. Ghosh M et al. Influence of physiological changes in endogenous estrogen on circulating PCSK9 and LDL cholesterol. J Lipid Res. 56, 463-9 (2015),
  13. Huijgen R et al. Plasma levels of proprotein convertase subtilisin Kexin type 9 (PCSK9) and phenotypic variability in familial hypercholesterolemia. J Lipid Res. 53, 979-83 (2012)
  14. Hyrina A et al. 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. EBioMedicine. 23, 68-78 (2017)
  15. Iggman D et al. Role of dietary fats in modulating cardiometabolic risk during moderate weight gain: a randomized double-blind overfeeding trial (LIPOGAIN study). J Am Heart Assoc. 3, e001095 (2014),
  16. Jamie Cameron et al. Serum levels of proprotein convertase subtilisin/kexin type 9 in subjects with familial hypercholesterolemia indicate that proprotein convertase subtilisin/kexin type 9 is cleared from plasma by low-density lipoprotein receptor_independent pathways. Translational Research. 160: 125-30. 2012,
  17. Jia YJ et al. Short- and long-term effects of Xuezhikang (), an extract of cholestin, on serum proprotein convertase subtilisin/kexin type 9 levels. Chin J Integr Med. (2014),
  18. Kawashiri MA et al. Efficacy and Safety of Coadministration of Rosuvastatin, Ezetimibe, and Colestimide in Heterozygous Familial Hypercholesterolemia. Am J Cardiol. 109: 364-9. 2011,
  19. Lambert G et al. Elevated plasma PCSK9 level is equally detrimental for patients with nonfamilial hypercholesterolemia and heterozygous familial hypercholesterolemia, irrespective of low-density lipoprotein receptor defects. J Am Coll Cardiol. 63, 2365-73 (2014),
  20. Le Bras M et al. Plasma PCSK9 is a late biomarker of severity in patients with severe trauma injury. J Clin Endocrinol Metab. 98, E732-6 (2013),
  21. Lee CJ et al. Association of serum proprotein convertase subtilisin/kexin type 9 with carotid intima media thickness in hypertensive subjects. Metabolism. 62, 845-50 (2013),
  22. Lena Persson. Studies on PCSK9 in the regulation of cholesterol metabolism. Published by Karolinska Institutet. Stockholm 2011,
  23. Li S et al. Novel and traditional lipid-related biomarkers and their combinations in predicting coronary severity. Sci Rep. 7, 360 (2017)
  24. Li S et al. Novel circulating lipid measurements for current dyslipidemias in non-treated patients undergoing coronary angiography:PSCK9,  apoC3 and sdLDL-C. Oncotarget 8, 12333-12341 (2017)
  25. Lindholm MW et al. PCSK9 LNA Antisense Oligonucleotides Induce Sustained Reduction of LDL Cholesterol in Nonhuman Primates. Mol Ther. 20: 376-81. 2012,
  26. Mayne J et al. Differential effects of PCSK9 loss of function variants on serum lipid and PCSK9 levels in Caucasian and African Canadian populations. Lipids Health Dis. 12, 70 (2013),
  27. Mayne J et al. 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. Clin Chem. 57: 1415, 2011,
  28. Mayne J et al. 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. Clin Chem. 57,1415 (2011)
  29. Mbikay M et al. Quercetin-3-glucoside increases low-density lipoprotein receptor (LDLR) expression, attenuates proprotein convertase subtilisin/kexin 9 (PCSK9) secretion, and stimulates LDL uptake by Huh7 human hepatocytes in culture. FEBS Open Bio. 4, 755-62 (2014),
  30. Miasan A et al. Effects of LDL Receptor Modulation on Lymphatic Function. Sci Rep. 6, 27862 (2016)
  31. Navarese EP et al. Association of PCKS9 with platelet reactivity in patients with acute coronary syndrome treated with prasugrel or ticagrelor: The PCSK9 REACT study. Int J Cardiol. 227, 644-649 (2017)
  32. Noguchi T et al. Comparison of effects of bezafibrate and fenofibrate on circulating proprotein convertase subtilisin/kexin type 9 and adipocytokine levels in dyslipidemic subjects with impaired glucose tolerance or type 2 diabetes mellitus: Results from a crossover study. Atherosclerosis 217: 165-70, 2011,
  33. Noguchi T et al. The E32K variant of PCSK9 exacerbates the phenotype of familial hypercholesterolaemia by increasing PCSK9 function and concentration in the circulation. Atherosclerosis 210, 166-172 (2010)
  34. P. Costet et al. Plasma PCSK9 is increased by Fenofibrate and Atorvastatin in a non additive fashion in diabetic patients. Atherosclerosis 212: 246-251, 2010,
  35. Persson L et al. Endogenous Estrogens Lower Plasma PCSK9 and LDL Cholesterol But Not Lp(a) or Bile Acid Synthesis in Women. Arterioscler Thromb Vasc Biol. 32: 810-4. 2011,
  36. Peticca P et al. 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. ISRN Endocrinol. 2013, 341632 (2013),
  37. Rogacev KS et al. PCSK9 Plasma Concentrations Are Independent of GFR and Do Not Predict Cardiovascular Events in Patients with Decreased GFR. PLoS One 11, e0146920 (2016)
  38. Rosqvist F et al. Potential role of milk fat globule membrane in modulating plasma lipoproteins, gene expression, and cholesterol metabolism in humans: a randomized study. Am J Clin Nutr. 102, 20-30 (2015)
  39. Si-Tayeb K et al. Urine-sample-derived human induced pluripotent stem cells as a model to study PCSK9-mediated autosomal dominant hypercholesterolemia. Dis Model Mech. 9, 81-90 (2016)
  40. Starr AE et al. β-Estradiol results in a proprotein convertase subtilisin/kexin type 9-dependent increase in low-density lipoprotein receptor levels in human hepatic HuH7 cells. FEBS J. 282, 2682-96 (2015)
  41. Suzuki Y et al. Biodegradable lipid nanoparticles induce a prolonged RNA interference-mediated protein knockdown and show rapid hepatic clearance in mice and nonhuman primates. Int J Pharm. 519, 34-43 (2017)
  42. Tohru Noguchi et al. The E32K variant of PCSK9 exacerbates the phenotype of familial hypercholesterolaemia by increasing PCSK9 function and concentration in the circulation. Atherosclerosis. 210: 166-172, 2010,
  43. Tremblay AJ et al. Short-term, high-fat diet increases the expression of key intestinal genes involved in lipoprotein metabolism in healthy men. Am J Clin Nutr. 98, 32-41 (2013),
  44. van Pelgeest EP et al. Antisense-mediated reduction of proprotein convertase subtilisin/kexin type 9 (PCSK9): a first-in-human randomized, placebo-controlled trial. Br J Clin Pharmacol. 80, 1350-61 (2015)
  45. Vergès B et al. Lack of association between plasma PCSK9 and LDL-apoB100 catabolism in patients with uncontrolled type 2 diabetes. Atherosclerosis. 219: 342-8. 2011,
  46. Vlachopopulos C et al. Prediction of cardiovascular events with levels of proprotein convertase subtilisin/kexin type 9: A systematic review and meta-analysis. Atherosclerosis. 252, 50-60 (2016)
  47. Wassef H et al. The apoB-to-PCSK9 ratio: A new index for metabolic risk in humans. J Clin Lipidol. 9, 664-75 (2015)
  48. Werner C et al. Risk prediction with proprotein convertase subtilisin/kexin type 9 (PCSK9) in patients with stable coronary disease on statin treatment. Vascul Pharmacol. 62, 94-102 (2014),
  49. Xu RX et al. Relation of plasma PCSK9 levels to lipoprotein subfractions in patients with stable coronary artery disease. Lipids Health Dis. 13, 188 (2014)
  50. Xu RX et al. Impacts of ezetimibe on PCSK9 in rats: study on the expression in different organs and the potential mechanisms. J Transl Med. 13, 87 (2015)
References
  1. Seidah NG, Benjannet S, Wickham L, Marcinkiewicz J, Jasmin SB, Stifani S, Basak A, Prat A, Chretien M (2003) Proc Natl Acad Sci USA 100:928–933.
  2. Abifadel M, Varret M, Rabes JP, Allard D, Ouguerram K, Devillers M, Cruaud C, Benjannet S, Wickham L, Erlich D, et al. (2003) Nat Genet 34:154–156.
  3. Leren TP (2004) Clin Genet 65:419–422.
  4. Allard D, Amsellem S, Abifadel M, Trillard M, Devillers M, Luc G, Krempf M, Reznik Y, Girardet JP, Fredenrich A, et al. (2005) Hum Mutat 26:497.
  5. Cohen JC, Boerwinkle E, Mosley TH, Jr, Hobbs HH (2006) N Engl J Med 354, 1264–1272.
  6. Berge KE, Ose L, Leren TP (2006) Arterioscler Thromb Vasc Biol 26:1094–1100.
  7. Maxwell KN, Breslow JL (2004) Proc Natl Acad Sci USA 101:7100–7105.
  8. Rashid S, Curtis DE, Garuti R, Anderson NN, Bashmakov Y, Ho YK, Hammer RE, Moon YA, Horton JD (2005) Proc Natl Acad Sci USA 102:5374–5379.
  9. Lagace, T. A., Curtis, D. E., Garuti, R., McNutt, M. C., Park, S. W., Prather, H. B., Anderson, N. N., Ho, Y. K., Hammer, R. E., and Horton, J. D. (2006) J. Clin. Investig. 116, 2995–3005
  10. Cameron, J., Holla, O. L., Ranheim, T., Kulseth, M. A., Berge, K. E., and Leren, T. P. (2006) Hum. Mol. Genet. 15, 1551–1558
  11. Zhang, D. W., Lagace, T. A., Garuti, R., Zhao, Z., McDonald, M., Horton, J. D., Cohen, J. C., and Hobbs, H. H. (2007) J. Biol. Chem. 282, 18602–18612