OpenLB
Open Library of Bioscience
Advanced Search
Communications biology
08 13, 2024;7 (1): 985.

Contrasting effects of intracellular and extracellular human PCSK9 on inflammation, lipid alteration and cell death.

Aram Ghalali, Fahd Alhamdan, Swapna Upadhyay, Koustav Ganguly, Kjell Larsson, Lena Palmberg, Mizanur Rahman
Author Information
  1. Aram Ghalali: Vascular Biology Program, Boston Children Hospital, Harvard Medical school, Boston, MA, USA.
  2. Fahd Alhamdan: Department of Anesthesiology, Critical Care, and Pain Medicine, Cardiac Anesthesia Division, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
  3. Swapna Upadhyay: Unit of Integrative Toxicology, Institute of Environmental Medicine, Karolinska Insitutet, Stockholm, Sweden.
  4. Koustav Ganguly: Unit of Integrative Toxicology, Institute of Environmental Medicine, Karolinska Insitutet, Stockholm, Sweden.
  5. Kjell Larsson: Unit of Integrative Toxicology, Institute of Environmental Medicine, Karolinska Insitutet, Stockholm, Sweden.
  6. Lena Palmberg: Unit of Integrative Toxicology, Institute of Environmental Medicine, Karolinska Insitutet, Stockholm, Sweden.
  7. Mizanur Rahman: Unit of Integrative Toxicology, Institute of Environmental Medicine, Karolinska Insitutet, Stockholm, Sweden. mizanur.rahman@ki.se. ORCID
PMID: 39138259 DOI: 10.1038/s42003-024-06674-9

Abstract

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is one of the major regulators of low-density lipoprotein receptor (LDLR). Information on role and regulation of PCSK9 in lung is very limited. Our study focuses on understanding the role and regulation of PCSK9 in the lung. PCSK9 levels are higher in Bronchoalveolar lavage fluid (BALF) of smokers with or without chronic obstructive pulmonary diseases (COPD) compared to BALF of nonsmokers. PCSK9-stimulated cells induce proinflammatory cytokines and activation of MAPKp38. PCSK9 transcripts are highly expressed in healthy individuals compared to COPD, pulmonary fibrosis or pulmonary systemic sclerosis. Cigarette smoke extract reduce PCSK9 levels in undifferentiated pulmonary bronchial epithelial cells (PBEC) but induce in differentiated PBEC. PCSK9 inhibition affect biological pathways, induces lipid peroxidation, and higher level of apoptosis in response to staurosporine. Our results suggest that higher levels of PCSK9 in BALF acts as an inflammatory marker. Furthermore, extracellular and intracellular PCSK9 play different roles.

References

  1. Lipids Health Dis. 2022 Jan 7;21(1):3 [PMID: 34996457]
  2. Nat Rev Endocrinol. 2018 Dec;15(1):52-62 [PMID: 30367179]
  3. Cell Death Dis. 2022 Jul 26;13(7):649 [PMID: 35882850]
  4. J Am Coll Cardiol. 2023 Jan 24;81(3):224-234 [PMID: 36653090]
  5. Cardiovasc Res. 2016 Oct;112(1):429-42 [PMID: 27496869]
  6. Respir Med. 2011 Aug;105(8):1222-30 [PMID: 21439805]
  7. Cardiovasc Drugs Ther. 2023 May 31;: [PMID: 37256417]
  8. Mol Cancer. 2017 Jan 19;16(1):14 [PMID: 28103884]
  9. Cells. 2022 Dec 23;12(1): [PMID: 36611859]
  10. Chest. 2005 Jun;127(6):1952-9 [PMID: 15947307]
  11. Commun Biol. 2024 Jan 2;7(1):8 [PMID: 38168942]
  12. Sci Rep. 2022 Sep 30;12(1):16396 [PMID: 36180488]
  13. Sci Rep. 2020 Nov 24;10(1):20460 [PMID: 33235237]
  14. Arthritis Res Ther. 2021 Jan 19;23(1):32 [PMID: 33461620]
  15. Nat Genet. 2003 Jun;34(2):154-6 [PMID: 12730697]
  16. Viruses. 2021 Dec 17;13(12): [PMID: 34960806]
  17. Signal Transduct Target Ther. 2021 Mar 6;6(1):111 [PMID: 33677469]
  18. J Inflamm (Lond). 2023 Nov 17;20(1):39 [PMID: 37978397]
  19. Eur J Med Res. 2023 Mar 20;28(1):127 [PMID: 36935521]
  20. Respir Res. 2022 Jul 8;23(1):180 [PMID: 35804363]
  21. Exp Hematol Oncol. 2021 Mar 31;10(1):25 [PMID: 33789749]
  22. Toxics. 2023 Jun 14;11(6): [PMID: 37368632]
  23. Exp Ther Med. 2017 May;13(5):1993-1999 [PMID: 28565798]
  24. Expert Opin Drug Saf. 2022 Jan;21(1):9-20 [PMID: 34596005]
  25. Aust Prescr. 2016 Oct;39(5):164-167 [PMID: 27789927]
  26. Am J Respir Cell Mol Biol. 2021 Apr;64(4):426-440 [PMID: 33444514]
  27. Sci Adv. 2020 Jul 08;6(28):eaba1972 [PMID: 32832598]
  28. Proc Natl Acad Sci U S A. 2003 Feb 4;100(3):928-33 [PMID: 12552133]
  29. Oncogene. 2006 Mar 13;25(11):1679-91 [PMID: 16550168]
  30. Sci Adv. 2020 Jul 08;6(28):eaba1983 [PMID: 32832599]
  31. Am J Physiol Lung Cell Mol Physiol. 2016 Feb 15;310(4):L377-86 [PMID: 26719146]
  32. Lupus. 2020 Jul;29(8):825-835 [PMID: 32479241]
  33. Ann Rheum Dis. 2019 Oct;78(10):1379-1387 [PMID: 31405848]
  34. Lipids Health Dis. 2018 Nov 21;17(1):263 [PMID: 30463568]
  35. Atherosclerosis. 2024 May;392:117529 [PMID: 38583289]
  36. Am J Physiol Lung Cell Mol Physiol. 2014 Jun 1;306(11):L1006-15 [PMID: 24705725]
  37. J Thorac Dis. 2020 May;12(5):2791-2802 [PMID: 32642187]
  38. COPD. 2010 Feb;7(1):5-10 [PMID: 20214458]
  39. Clin Immunol. 2016 May;166-167:27-37 [PMID: 27102765]
  40. Front Med (Lausanne). 2022 Jun 13;9:876046 [PMID: 35770004]
  41. Cardiovasc Res. 2020 Apr 1;116(5):908-915 [PMID: 31746997]
  42. Transl Res. 2016 Jul;173:19-29 [PMID: 26548330]
  43. Sci Immunol. 2023 Apr 14;8(82):eadd8945 [PMID: 37027478]
  44. Mucosal Immunol. 2021 Sep;14(5):978-990 [PMID: 33608655]
  45. Nat Commun. 2022 Jul 8;13(1):3971 [PMID: 35803966]
  46. Molecules. 2022 Jan 10;27(2): [PMID: 35056760]
  47. Nature. 2020 Dec;588(7839):693-698 [PMID: 33177715]
  48. Sci Rep. 2018 Feb 2;8(1):2267 [PMID: 29396513]
  49. J Am Coll Cardiol. 2019 May 7;73(17):2166-2177 [PMID: 30846341]

MeSH Term

Humans
Proprotein Convertase 9
Inflammation
Bronchoalveolar Lavage Fluid
Pulmonary Disease, Chronic Obstructive
Cell Death
Lipid Metabolism
Male
Apoptosis
Epithelial Cells
Female

Chemicals

Proprotein Convertase 9
PCSK9 protein, human
Journal Article Research Support, Non-U.S. Gov't
Article has an altmetric score of 1

Word Cloud

Created with Highcharts 10.0.0PCSK9pulmonarylevelshigherBALFroleregulationlungCOPDcomparedcellsinducePBEClipidextracellularintracellularProproteinconvertasesubtilisin/kexintype9onemajorregulatorslow-densitylipoproteinreceptorLDLRInformationlimitedstudyfocusesunderstandingBronchoalveolarlavagefluidsmokerswithoutchronicobstructivediseasesnonsmokersPCSK9-stimulatedproinflammatorycytokinesactivationMAPKp38transcriptshighlyexpressedhealthyindividualsfibrosissystemicsclerosisCigarettesmokeextractreduceundifferentiatedbronchialepithelialdifferentiatedinhibitionaffectbiologicalpathwaysinducesperoxidationlevelapoptosisresponsestaurosporineresultssuggestactsinflammatorymarkerFurthermoreplaydifferentrolesContrastingeffectshumaninflammationalterationcelldeath

Similar Articles

Cited By