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PCSK9 and inflammation: a review of experimental and clinical evidence

Momtazi-Borojeni, Amir Abbas, Sabouri-Rad, Sarvenaz, Gotto, Antonio M, Pirro, Matteo, Banach, Maciej, Awan, Zuhier, Barreto, George E, Sahebkar, Amirhossein·2019·European Heart Journal - Cardiovascular Pharmacotherapy
DOI 10.1093/ehjcvp/pvz022
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Abstract

Proprotein convertase subtilisin/kexin Type 9 (PCSK9) is now identified as an important and major player in hypercholesterolaemia and atherosclerosis pathophysiology. PCSK9, through promoting lysosomal degradation of hepatic low-density lipoprotein (LDL) receptor, can decrease the clearance of plasma LDLs, leading to hypercholesterolaemia and consequent atherosclerotic plaque formation. Hypercholesterolaemia has been found to promote systemic and vascular inflammation, which can cause atherosclerotic lesion formation and progression and subsequent incidence of cardiovascular disease. Recent studies have shown the involvement of PCSK9 in the inflammatory pathway of atherosclerosis. Although trials with PCSK9 inhibitors have not shown any alteration in plasma C-reactive protein levels, there is accumulating evidence showing lessened inflammatory response in the arterial wall that could attenuate atherosclerotic plaque development beyond the established LDL-lowering effect of PCSK9 inhibition. In this review, we represent mounting evidence indicating that PCSK9 can locally increase vascular inflammation and contribute to atherosclerotic plaque progression in patients with hypercholesterolaemia.

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Research works printed but not linked: 62

  1. Ruparelia, 2017, Inflammatory processes in cardiovascular disease: a route to targeted therapies, Nat Rev Cardiol, 14, 133., 10.1038/nrcardio.2016.185 · DOI · Paper page
  2. Ross, 1993, The pathogenesis of atherosclerosis: a perspective for the 1990s, Nature, 362, 801., 10.1038/362801a0 · DOI
  3. Leitinger, 2003, Oxidized phospholipids as modulators of inflammation in atherosclerosis, Curr Opin Lipidol, 14, 421, 10.1097/00041433-200310000-00002 · DOI
  4. Borén, 1998, Identification of the principal proteoglycan-binding site in LDL. A single-point mutation in apo-B100 severely affects proteoglycan interaction without affecting LDL receptor binding, J Clin Invest, 101, 2658, 10.1172/JCI2265 · DOI
  5. Peiser, 2002, Scavenger receptors in innate immunity, Curr Opin Immunol, 14, 123, 10.1016/S0952-7915(01)00307-7 · DOI
  6. Awan, 2016, Reducing vascular calcification by anti-IL-1beta monoclonal antibody in a mouse model of familial hypercholesterolemia, Angiology, 67, 157, 10.1177/0003319715583205 · DOI
  7. Ridker, 2017, Antiinflammatory therapy with canakinumab for atherosclerotic disease, N Engl J Med, 377, 1119, 10.1056/NEJMoa1707914 · DOI · Paper page
  8. Lambert, 2009, Molecular basis of PCSK9 function, Atherosclerosis, 203, 1, 10.1016/j.atherosclerosis.2008.06.010 · DOI
  9. Lagace, 2014, PCSK9 and LDLR degradation: regulatory mechanisms in circulation and in cells, Curr Opin Lipidol, 25, 387, 10.1097/MOL.0000000000000114 · DOI · Paper page
  10. Schulz, 2015, Molecular and cellular function of the proprotein convertase subtilisin/kexin type 9 (PCSK9), Basic Res Cardiol, 110, 4., 10.1007/s00395-015-0463-z · DOI · Paper page
  11. Shapiro, 2017, PCSK9 and atherosclerosis-lipids and beyond, J Atheroscler Thromb, 24, 462, 10.5551/jat.RV17003 · DOI
  12. Li, 2014, Association of plasma PCSK9 levels with white blood cell count and its subsets in patients with stable coronary artery disease, Atherosclerosis, 234, 441, 10.1016/j.atherosclerosis.2014.04.001 · DOI
  13. Zhang, 2014, Relation of circulating PCSK9 concentration to fibrinogen in patients with stable coronary artery disease, J Clin Lipidol, 8, 494, 10.1016/j.jacl.2014.07.001 · DOI
  14. Gencer, 2016, Prognostic value of PCSK9 levels in patients with acute coronary syndromes, Eur Heart J, 37, 546, 10.1093/eurheartj/ehv637 · DOI
  15. Li, 2015, Proprotein convertase subtilisin-kexin type 9 as a biomarker for the severity of coronary artery disease, Ann Med, 47, 386, 10.3109/07853890.2015.1042908 · DOI
  16. Madjid, 2013, Components of the complete blood count as risk predictors for coronary heart disease: in-depth review and update, Tex Heart Inst J, 40, 17.
  17. Koenig, 2003, Fibrin (ogen) in cardiovascular disease: an update, Thromb Haemost, 89, 601, 10.1055/s-0037-1613566 · DOI
  18. Pearson, 2004, CDC/AHA workshop on markers of inflammation and cardiovascular disease, Circulation, 110, e543, 10.1161/01.CIR.0000148979.11121.6B · DOI
  19. Danesh, 2005, Plasma fibrinogen level and the risk of major cardiovascular diseases and nonvascular mortality: an individual participant meta-analysis, JAMA, 294, 1799
  20. Du Clos, 2000, Function of C-reactive protein, Ann Med, 32, 274, 10.3109/07853890009011772 · DOI
  21. Zhang, 1999, Coronary C-reactive protein distribution: its relation to development of atherosclerosis, Atherosclerosis, 145, 375, 10.1016/S0021-9150(99)00105-7 · DOI
  22. Jialal, 2004, C-reactive protein: risk marker or mediator in atherothrombosis?, Hypertension, 44, 6, 10.1161/01.HYP.0000130484.20501.df · DOI
  23. Kaptoge, 2010, C-reactive protein concentration and risk of coronary heart disease, stroke, and mortality: an individual participant meta-analysis, Lancet, 375, 132, 10.1016/S0140-6736(09)61717-7 · DOI · Paper page
  24. Ridker, 2000, C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women, N Engl J Med, 342, 836, 10.1056/NEJM200003233421202 · DOI · Paper page
  25. 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
  26. Walley, 2014, PCSK9 is a critical regulator of the innate immune response and septic shock outcome, Sci Transl Med, 6, 258ra143, 10.1126/scitranslmed.3008782 · DOI
  27. Tang, 2015, TLR4/NF-κB signaling contributes to chronic unpredictable mild stress-induced atherosclerosis in ApoE-/- mice, PLoS One, 10, e0123685., 10.1371/journal.pone.0123685 · DOI
  28. Monaco, 2004, Nuclear factor κB: a potential therapeutic target in atherosclerosis and thrombosis, Cardiovasc Res, 61, 671, 10.1016/j.cardiores.2003.11.038 · DOI
  29. Chen, 1999, New insights into the role of nuclear factor-κB, a ubiquitous transcription factor in the initiation of diseases, Clin Chem, 45, 7, 10.1093/clinchem/45.1.7 · DOI
  30. De Winther, 2005, Nuclear factor κB signaling in atherogenesis, Arterioscler Thromb Vasc Biol, 25, 904, 10.1161/01.ATV.0000160340.72641.87 · DOI
  31. Tang, 2017, New role of PCSK9 in atherosclerotic inflammation promotion involving the TLR4/NF-κB pathway, Atherosclerosis, 262, 113, 10.1016/j.atherosclerosis.2017.04.023 · DOI · Paper page
  32. Tang, 2012, PCSK9 siRNA suppresses the inflammatory response induced by oxLDL through inhibition of NF-κB activation in THP-1-derived macrophages, Int J Mol Med, 30, 931, 10.3892/ijmm.2012.1072 · DOI · Paper page
  33. Cominacini, 2000, Oxidized low density lipoprotein (ox-LDL) binding to ox-LDL receptor-1 in endothelial cells induces the activation of NF-κB through an increased production of intracellular reactive oxygen species, J Biol Chem, 275, 12633, 10.1074/jbc.275.17.12633 · DOI
  34. Feingold, 2008, Inflammation stimulates the expression of PCSK9, Biochem Biophys Res Commun, 374, 341, 10.1016/j.bbrc.2008.07.023 · DOI
  35. Kawai, 2007, Signaling to NF-κB by Toll-like receptors, Trends Mol Med, 13, 460, 10.1016/j.molmed.2007.09.002 · DOI
  36. Ferri, 2012, Proprotein convertase subtilisin kexin type 9 (PCSK9) secreted by cultured smooth muscle cells reduces macrophages LDLR levels, Atherosclerosis, 220, 381, 10.1016/j.atherosclerosis.2011.11.026 · DOI
  37. Ferri, 2016, PCSK9 knock-out mice are protected from neointimal formation in response to perivascular carotid collar placement, Atherosclerosis, 253, 214, 10.1016/j.atherosclerosis.2016.07.910 · DOI
  38. Ding, 2015, Hemodynamic shear stress via ROS modulates PCSK9 expression in human vascular endothelial and smooth muscle cells and along the mouse aorta, Antioxid Redox Signal, 22, 760, 10.1089/ars.2014.6054 · DOI
  39. Brandes, 2005, Vascular NADPH oxidases: molecular mechanisms of activation, Cardiovasc Res, 65, 16, 10.1016/j.cardiores.2004.08.007 · DOI
  40. Pirillo, 2013, LOX-1, OxLDL, and atherosclerosis, Mediators Inflamm, 2013, 1., 10.1155/2013/152786 · DOI
  41. Ding, 2015, Cross-talk between LOX-1 and PCSK9 in vascular tissues, Cardiovasc Res, 107, 556, 10.1093/cvr/cvv178 · DOI
  42. Mehta, 2007, Deletion of LOX-1 reduces atherogenesis in LDLR knockout mice fed high cholesterol diet, Circ Res, 100, 1634, 10.1161/CIRCRESAHA.107.149724 · DOI
  43. Ding, 2016, Cross-talk between PCSK9 and damaged mtDNA in vascular smooth muscle cells: role in apoptosis, Antioxid Redox Signal, 25, 997, 10.1089/ars.2016.6631 · DOI
  44. Denis, 2012, Gene inactivation of proprotein convertase subtilisin/kexin type 9 reduces atherosclerosis in mice clinical perspective, Circulation, 125, 894, 10.1161/CIRCULATIONAHA.111.057406 · DOI · Paper page
  45. Ason, 2014, PCSK9 inhibition fails to alter hepatic LDLR, circulating cholesterol, and atherosclerosis in the absence of ApoE, J Lipid Res, 55, 2370, 10.1194/jlr.M053207 · DOI
  46. Giunzioni, 2016, Local effects of human PCSK9 on the atherosclerotic lesion, J Pathol, 238, 52, 10.1002/path.4630 · DOI
  47. Grune, 2017, PCSK9 regulates the chemokine receptor CCR2 on monocytes, Biochem Biophys Res Commun, 485, 312, 10.1016/j.bbrc.2017.02.085 · DOI
  48. Guo, 2009, Leucocyte cathepsin K affects atherosclerotic lesion composition and bone mineral density in low-density lipoprotein receptor deficient mice, Cardiovasc Res, 81, 278, 10.1093/cvr/cvn311 · DOI
  49. Shah, 2009, Inflammation and plaque vulnerability, Cardiovasc Drugs Ther, 23, 31, 10.1007/s10557-008-6147-2 · DOI
  50. Momtazi-Borojeni, 2019, Long-term generation of antiPCSK9 antibody using a nanoliposome-based vaccine delivery system, Atherosclerosis, 283, 69, 10.1016/j.atherosclerosis.2019.02.001 · DOI
  51. Momtazi-Borojeni, 2019, Potential anti-tumor effect of a nanoliposomal antiPCSK9 vaccine in mice bearing colorectal cancer, Arch Med Sci, 15, 559, 10.5114/aoms.2019.84732 · DOI
  52. Momtazi-Borojeni, 2019, Effects of immunization against PCSK9 in an experimental model of breast cancer, Arch Med Sci, 15, 570, 10.5114/aoms.2019.84734 · DOI
  53. Landlinger, 2017, The AT04A vaccine against proprotein convertase subtilisin/kexin type 9 reduces total cholesterol, vascular inflammation, and atherosclerosis in APOE* 3Leiden.CETP mice, Eur Heart J, 38, 2499, 10.1093/eurheartj/ehx260 · DOI
  54. Swirski, 2007, Ly-6Chi monocytes dominate hypercholesterolemia-associated monocytosis and give rise to macrophages in atheromata, J Clin Invest, 117, 195., 10.1172/JCI29950 · DOI
  55. Abela, 2010, Cholesterol crystals piercing the arterial plaque and intima trigger local and systemic inflammation, J Clin Lipidol, 4, 156, 10.1016/j.jacl.2010.03.003 · DOI
  56. Libby, 2006, Plaque stabilization: can we turn theory into evidence?, Am J Cardiol, 98, S26, 10.1016/j.amjcard.2006.09.017 · DOI
  57. Bernelot Moens, 2017, PCSK9 monoclonal antibodies reverse the pro-inflammatory profile of monocytes in familial hypercholesterolaemia, Eur Heart J, 38, 1584, 10.1093/eurheartj/ehx002 · DOI
  58. Baruch, 2017, Effects of RG7652, a monoclonal antibody against PCSK9, on LDL-C, LDL-C subfractions, and inflammatory biomarkers in patients at high risk of or with established coronary heart disease (from the Phase 2 EQUATOR Study), Am J Cardiol, 119, 1576, 10.1016/j.amjcard.2017.02.020 · DOI
  59. Pradhan, 2018, Residual inflammatory risk on treatment with PCSK9 inhibition and statin therapy, Circulation, 138, 141, 10.1161/CIRCULATIONAHA.118.034645 · DOI · Paper page
  60. Sahebkar, 2016, Effect of monoclonal antibodies to PCSK9 on high-sensitivity C-reactive protein levels: a meta-analysis of 16 randomized controlled treatment arms, Br J Clin Pharmacol, 81, 1175, 10.1111/bcp.12905 · DOI · Paper page
  61. Signorelli, 2012, Inflammation in peripheral arterial disease (PAD), Curr Pharm Des, 18, 4350, 10.2174/138161212802481273 · DOI
  62. Bonaca, 2018, Low-density lipoprotein cholesterol lowering with evolocumab and outcomes in patients with peripheral artery disease: insights from the FOURIER Trial (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk), Circulation, 137, 338, 10.1161/CIRCULATIONAHA.117.032235 · DOI · Paper page

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Metadata

Authors
Momtazi-Borojeni, A. A., Sabouri-Rad, S., Gotto, A. M., Pirro, M., Banach, M., Awan, Z., Barreto, G. E., & Sahebkar, A.
Affiliations
  • Nanotechnology Research Center, Bu-Ali Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran
  • School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
  • Weill Cornell Medical College, New York, NY, USA
  • Unit of Internal Medicine, Angiology and Arteriosclerosis Diseases, Department of Medicine, University of Perugia, Perugia, Italy
  • Department of Hypertension, WAM University Hospital in Lodz, Medical University of Lodz, Zeromskiego 113, Lodz, Poland
  • Department of Clinical Biochemistry, King Abdulaziz University, Jeddah, Saudi Arabia
  • Departamento de Nutrición y Bioquímica, Facultad de Ciencias, Pontificia Universidad Javeriana, Bogotá D.C., Colombia
  • Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
ORCID
Sahebkar, Amirhossein
Venue
European Heart Journal - Cardiovascular Pharmacotherapy
Publisher
Oxford University Press (OUP)
Published
2019-06-25
Volume
5
Issue
4
Pages
237-245
ISSN
  • 2055-6837
  • 2055-6845
DOI
10.1093/ehjcvp/pvz022
Cited by
188
References
5
Language
en
Licence
academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
Funders
  • National Institute for Medical Research Development
  • NIMAD (963401)

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