Skip to main content
SpringerLink
Log in
Book cover

The Role of Bioactive Lipids in Cancer, Inflammation and Related Diseases pp 65–75Cite as

Novel n-3 Docosapentaneoic Acid-Derived Pro-resolving Mediators Are Vasculoprotective and Mediate the Actions of Statins in Controlling Inflammation

  • Chapter
  • First Online:

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1161))

Abstract

Inflammation is a fundamentally protective process that guards the host from invading pathogens and is central in the repair and regeneration of damaged tissue. However, when uncontrolled, the overzealous response leads to tissue damage and malaise. Indeed, this process is now appreciated to be at the center of many chronic inflammatory diseases including vascular disease and arthritis. Studies investigating the mechanisms through which acute inflammation is actively turned off allowing tissues to regain function demonstrated that the essential fatty acids, arachidonic acid (AA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are enzymatically converted to bioactive mediators. These autacoids carry distinct structures and biological actions, actively reprogramming the inflammatory reaction to promote its termination by counter-regulating the production of pro-inflammatory mediators and regulate leukocyte trafficking as well as phenotype. Recently we found that n-3 docosapentaenoic acid (DPA), which was until then only regarded as a biosynthetic intermediate in the formation of DHA from EPA, is also converted to structurally distinct bioactive mediators that reprogram the host immune response. In the present review we will discuss the evidence underpinning the biological actions of these novel n-3 DPA-derived autacoids in particular as they pertain to the vascular system.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  1. Malagoli D (2016) The evolution of the immune system: conservation and diversification. Elsevier, Amsterdam

    Chapter  Google Scholar 

  2. Majno G (1991) The ancient riddle of sigma eta psi iota sigma (sepsis). J Infect Dis 163(5):937–945

    Article  CAS  PubMed  Google Scholar 

  3. Dalli J, Serhan CN (2018) Identification and structure elucidation of the pro-resolving mediators provides novel leads for resolution pharmacology. Br J Pharmacol 176:1024–1037. https://doi.org/10.1111/bph.14336

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. de Gaetano M, McEvoy C, Andrews D, Cacace A, Hunter J, Brennan E, Godson C (2018) Specialized pro-resolving lipid mediators: modulation of diabetes-associated cardio-, reno-, and retino-vascular complications. Front Pharmacol 9:1488. https://doi.org/10.3389/fphar.2018.01488

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Perretti M, Norling LV (2017) Actions of SPM in regulating host responses in arthritis. Mol Asp Med 58:57–64. https://doi.org/10.1016/j.mam.2017.04.005

    Article  CAS  Google Scholar 

  6. Quiros M, Nusrat A (2019) Saving problematic mucosae: SPMs in intestinal mucosal inflammation and repair. Trends Mol Med 25:124–135. https://doi.org/10.1016/j.molmed.2018.12.004

    Article  CAS  PubMed  Google Scholar 

  7. Serhan CN, Levy BD (2018) Resolvins in inflammation: emergence of the pro-resolving superfamily of mediators. J Clin Invest 128(7):2657–2669. https://doi.org/10.1172/JCI97943

    Article  PubMed  PubMed Central  Google Scholar 

  8. Serhan CN (2017) Discovery of specialized pro-resolving mediators marks the dawn of resolution physiology and pharmacology. Mol Asp Med 58:1–11. https://doi.org/10.1016/j.mam.2017.03.001

    Article  Google Scholar 

  9. Serhan CN, Clish CB, Brannon J, Colgan SP, Chiang N, Gronert K (2000) Novel functional sets of lipid-derived mediators with antiinflammatory actions generated from omega-3 fatty acids via cyclooxygenase 2-nonsteroidal antiinflammatory drugs and transcellular processing. J Exp Med 192(8):1197–1204

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Serhan CN, Hong S, Gronert K, Colgan SP, Devchand PR, Mirick G, Moussignac RL (2002) Resolvins: a family of bioactive products of omega-3 fatty acid transformation circuits initiated by aspirin treatment that counter proinflammation signals. J Exp Med 196(8):1025–1037

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Serhan CN, Yang R, Martinod K, Kasuga K, Pillai PS, Porter TF, Oh SF, Spite M (2009) Maresins: novel macrophage mediators with potent antiinflammatory and proresolving actions. J Exp Med 206(1):15–23. https://doi.org/10.1084/jem.20081880

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Dona M, Fredman G, Schwab JM, Chiang N, Arita M, Goodarzi A, Cheng G, von Andrian UH, Serhan CN (2008) Resolvin E1, an EPA-derived mediator in whole blood, selectively counterregulates leukocytes and platelets. Blood 112(3):848–855. https://doi.org/10.1182/blood-2007-11-122598

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Morita M, Kuba K, Ichikawa A, Nakayama M, Katahira J, Iwamoto R, Watanebe T, Sakabe S, Daidoji T, Nakamura S, Kadowaki A, Ohto T, Nakanishi H, Taguchi R, Nakaya T, Murakami M, Yoneda Y, Arai H, Kawaoka Y, Penninger JM, Arita M, Imai Y (2013) The lipid mediator protectin D1 inhibits influenza virus replication and improves severe influenza. Cell 153(1):112–125. https://doi.org/10.1016/j.cell.2013.02.027

    Article  CAS  PubMed  Google Scholar 

  14. Dalli J, Vlasakov I, Riley IR, Rodriguez AR, Spur BW, Petasis NA, Chiang N, Serhan CN (2016) Maresin conjugates in tissue regeneration biosynthesis enzymes in human macrophages. Proc Natl Acad Sci U S A 113(43):12232–12237. https://doi.org/10.1073/pnas.1607003113

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Chiang N, Serhan CN (2017) Structural elucidation and physiologic functions of specialized pro-resolving mediators and their receptors. Mol Asp Med 58:114–129. https://doi.org/10.1016/j.mam.2017.03.005

    Article  CAS  Google Scholar 

  16. Colas RA, Dalli J, Chiang N, Vlasakov I, Sanger JM, Riley IR, Serhan CN (2016) Identification and actions of the Maresin 1 metabolome in infectious inflammation. J Immunol 197(11):4444–4452. https://doi.org/10.4049/jimmunol.1600837

    Article  CAS  PubMed  Google Scholar 

  17. Calder PC (2011) Fatty acids and inflammation: the cutting edge between food and pharma. Eur J Pharmacol 668(Suppl 1):S50–S58. https://doi.org/10.1016/j.ejphar.2011.05.085

    Article  CAS  PubMed  Google Scholar 

  18. De Caterina R (2011) n-3 fatty acids in cardiovascular disease. N Engl J Med 364(25):2439–2450. https://doi.org/10.1056/NEJMra1008153

    Article  PubMed  Google Scholar 

  19. Crawford MA, Broadhurst CL, Guest M, Nagar A, Wang Y, Ghebremeskel K, Schmidt WF (2013) A quantum theory for the irreplaceable role of docosahexaenoic acid in neural cell signalling throughout evolution. Prostaglandins Leukot Essent Fatty Acids 88(1):5–13. https://doi.org/10.1016/j.plefa.2012.08.005

    Article  CAS  PubMed  Google Scholar 

  20. Dalli J, Colas RA, Serhan CN (2013) Novel n-3 immunoresolvents: structures and actions. Sci Rep 3:1940. https://doi.org/10.1038/srep01940

    Article  PubMed  PubMed Central  Google Scholar 

  21. Lemaitre RN, Tanaka T, Tang W, Manichaikul A, Foy M, Kabagambe EK, Nettleton JA, King IB, Weng LC, Bhattacharya S, Bandinelli S, Bis JC, Rich SS, Jacobs DR Jr, Cherubini A, McKnight B, Liang S, Gu X, Rice K, Laurie CC, Lumley T, Browning BL, Psaty BM, Chen YD, Friedlander Y, Djousse L, Wu JH, Siscovick DS, Uitterlinden AG, Arnett DK, Ferrucci L, Fornage M, Tsai MY, Mozaffarian D, Steffen LM (2011) Genetic loci associated with plasma phospholipid n-3 fatty acids: a meta-analysis of genome-wide association studies from the CHARGE consortium. PLoS Genet 7(7):e1002193. https://doi.org/10.1371/journal.pgen.1002193

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Serhan CN, Savill J (2005) Resolution of inflammation: the beginning programs the end. Nat Immunol 6(12):1191–1197. https://doi.org/10.1038/ni1276

    Article  CAS  PubMed  Google Scholar 

  23. Aursnes M, Tungen JE, Vik A, Colas R, Cheng CY, Dalli J, Serhan CN, Hansen TV (2014) Total synthesis of the lipid mediator PD1n-3 DPA: configurational assignments and anti-inflammatory and pro-resolving actions. J Nat Prod 77(4):910–916. https://doi.org/10.1021/np4009865

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Gobbetti T, Dalli J, Colas RA, Federici Canova D, Aursnes M, Bonnet D, Alric L, Vergnolle N, Deraison C, Hansen TV, Serhan CN, Perretti M (2017) Protectin D1n-3 DPA and resolvin D5n-3 DPA are effectors of intestinal protection. Proc Natl Acad Sci U S A 114(15):3963–3968. https://doi.org/10.1073/pnas.1617290114

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Colas RA, Souza PR, Walker ME, Burton M, Zaslona Z, Curtis AM, Marques RM, Dalli J (2018) Impaired production and diurnal regulation of vascular RvDn-3 DPA increase systemic inflammation and cardiovascular disease. Circ Res 122(6):855–863. https://doi.org/10.1161/CIRCRESAHA.117.312472

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Ingle KA, Kain V, Goel M, Prabhu SD, Young ME, Halade GV (2015) Cardiomyocyte-specific Bmal1 deletion in mice triggers diastolic dysfunction, extracellular matrix response, and impaired resolution of inflammation. Am J Physiol Heart Circ Physiol 309(11):H1827–H1836. https://doi.org/10.1152/ajpheart.00608.2015

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. McAlpine CS, Swirski FK (2016) Circadian influence on metabolism and inflammation in atherosclerosis. Circ Res 119(1):131–141. https://doi.org/10.1161/CIRCRESAHA.116.308034

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Puttonen S, Oksanen T, Vahtera J, Pentti J, Virtanen M, Salo P, Kivimaki M (2010) Is shift work a risk factor for rheumatoid arthritis? The Finnish public sector study. Ann Rheum Dis 69(4):779–780. https://doi.org/10.1136/ard.2008.099184

    Article  PubMed  Google Scholar 

  29. Krump E, Picard S, Mancini J, Borgeat P (1997) Suppression of leukotriene B4 biosynthesis by endogenous adenosine in ligand-activated human neutrophils. J Exp Med 186(8):1401–1406

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Viola JR, Lemnitzer P, Jansen Y, Csaba G, Winter C, Neideck C, Silvestre-Roig C, Dittmar G, Doring Y, Drechsler M, Weber C, Zimmer R, Cenac N, Soehnlein O (2016) Resolving lipid mediators Maresin 1 and Resolvin D2 prevent atheroprogression in mice. Circ Res 119(9):1030–1038. https://doi.org/10.1161/CIRCRESAHA.116.309492

    Article  CAS  PubMed  Google Scholar 

  31. Fredman G, Hellmann J, Proto JD, Kuriakose G, Colas RA, Dorweiler B, Connolly ES, Solomon R, Jones DM, Heyer EJ, Spite M, Tabas I (2016) An imbalance between specialized pro-resolving lipid mediators and pro-inflammatory leukotrienes promotes instability of atherosclerotic plaques. Nat Commun 7:12859. https://doi.org/10.1038/ncomms12859

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Buckley CD, McGettrick HM (2018) Leukocyte trafficking between stromal compartments: lessons from rheumatoid arthritis. Nat Rev Rheumatol 14(8):476–487. https://doi.org/10.1038/s41584-018-0042-4

    Article  PubMed  Google Scholar 

  33. Tabas I, Lichtman AH (2017) Monocyte-macrophages and T cells in atherosclerosis. Immunity 47(4):621–634. https://doi.org/10.1016/j.immuni.2017.09.008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Pistorius K, Souza PR, De Matteis R, Austin-Williams S, Primdahl KG, Vik A, Mazzacuva F, Colas RA, Marques RM, Hansen TV, Dalli J (2018) PDn-3 DPA pathway regulates human monocyte differentiation and macrophage function. Cell Chem Biol 25(6):749–760 e749. https://doi.org/10.1016/j.chembiol.2018.04.017

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Primdahl KG, Tungen JE, De Souza PRS, Colas RA, Dalli J, Hansen TV, Vik A (2017) Stereocontrolled synthesis and investigation of the biosynthetic transformations of 16(S),17(S)-epoxy-PDn-3 DPA. Org Biomol Chem 15(40):8606–8613. https://doi.org/10.1039/c7ob02113e

    Article  CAS  PubMed  Google Scholar 

  36. Chiang N, Serhan CN (2017) Structural elucidation and physiologic functions of specialized pro-resolving mediators and their receptors. Mol Asp Med 58:114–129. https://doi.org/10.1016/j.mam.2017.03.005

    Article  CAS  Google Scholar 

  37. Dalli J, Serhan C (2016) Macrophage proresolving mediators-the when and where. Microbiol Spectr 4 (3). https://doi.org/10.1128/microbiolspec.MCHD-0001-2014

  38. Dalli J, Chiang N, Serhan CN (2015) Elucidation of novel 13-series resolvins that increase with atorvastatin and clear infections. Nat Med 21(9):1071–1075. https://doi.org/10.1038/nm.3911

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Primdahl KG, Aursnes M, Walker ME, Colas RA, Serhan CN, Dalli J, Hansen TV, Vik A (2016) Synthesis of 13(R)-Hydroxy-7Z,10Z,13R,14E,16Z,19Z Docosapentaenoic acid (13R-HDPA) and its biosynthetic conversion to the 13-series Resolvins. J Nat Prod 79(10):2693–2702. https://doi.org/10.1021/acs.jnatprod.6b00634

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Claria J, Serhan CN (1995) Aspirin triggers previously undescribed bioactive eicosanoids by human endothelial cell-leukocyte interactions. Proc Natl Acad Sci U S A 92(21):9475–9479

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Planaguma A, Pfeffer MA, Rubin G, Croze R, Uddin M, Serhan CN, Levy BD (2010) Lovastatin decreases acute mucosal inflammation via 15-epi-lipoxin A4. Mucosal Immunol 3(3):270–279. https://doi.org/10.1038/mi.2009.141

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Walker ME, Souza PR, Colas RA, Dalli J (2017) 13-series resolvins mediate the leukocyte-platelet actions of atorvastatin and pravastatin in inflammatory arthritis. FASEB J 31(8):3636–3648. https://doi.org/10.1096/fj.201700268

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Markworth JF, Kaur G, Miller EG, Larsen AE, Sinclair AJ, Maddipati KR, Cameron-Smith D (2016) Divergent shifts in lipid mediator profile following supplementation with n-3 docosapentaenoic acid and eicosapentaenoic acid. FASEB J 30(11):3714–3725. https://doi.org/10.1096/fj.201600360R

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK

    Jesmond Dalli, Kimberly Pistorius & Mary E. Walker

  2. Centre for Inflammation and Therapeutic Innovation, Queen Mary University of London, London, UK

    Jesmond Dalli

Authors
  1. Jesmond Dalli
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kimberly Pistorius
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mary E. Walker
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jesmond Dalli .

Editor information

Editors and Affiliations

  1. 431 Chemistry Building, Wayne State University, Detroit, MI, USA

    Kenneth V. Honn

  2. National Institutes of Health, Durham, NC, USA

    Darryl C. Zeldin

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Dalli, J., Pistorius, K., Walker, M.E. (2019). Novel n-3 Docosapentaneoic Acid-Derived Pro-resolving Mediators Are Vasculoprotective and Mediate the Actions of Statins in Controlling Inflammation. In: Honn, K., Zeldin, D. (eds) The Role of Bioactive Lipids in Cancer, Inflammation and Related Diseases. Advances in Experimental Medicine and Biology, vol 1161. Springer, Cham. https://doi.org/10.1007/978-3-030-21735-8_7

Download citation

Publish with us

Policies and ethics

Search

Navigation