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Specialized Pro-resolving Mediators Directs Cardiac Healing and Repair with Activation of Inflammation and Resolution Program in Heart Failure

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Book cover The Role of Bioactive Lipids in Cancer, Inflammation and Related Diseases

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

Abstract

After myocardial infarction, splenic leukocytes direct biosynthesis of specialized pro-resolving mediators (SPMs) that are essential for the resolution of inflammation and tissue repair. In a laboratory environment, after coronary ligation of healthy risk free rodents (young adult mice) leukocytes biosynthesize SPMs with induced activity of lipoxygenases and cyclooxygenases, which facilitate cardiac repair. Activated monocytes/macrophages drive the biosynthesis of SPMs following experimental myocardial infarction in mice during the acute heart failure. In the presented review, we provided the recent updates on SPMs (resolvins, lipoxins and maresins) in cardiac repair that may serve as novel therapeutics for future heart failure therapy/management. We incorporated the underlying causes of non-resolving inflammation following cardiac injury if superimposed with obesity, hypertension, diabetes, disrupted circadian rhythm, co-medication (painkillers or oncological therapeutics), and/or aging that may delay or impair the biosynthesis of SPMs, intensifying pathological remodeling in heart failure.

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Abbreviations

AA:

Arachidonic acid

AT-LXA4:

Aspirin-triggered LXA4

DHA:

docosahexaenoic acid

EPA:

eicosapentaenoic acid

H and E:

hematoxylin and eosin

HF:

heart failure

LV:

left ventricle

LX4:

lipoxin A4

LXB4:

lipoxin B4

MaR1:

maresin 1

MaR2:

maresin 2

MI:

myocardial infarction

RvD1:

resolvin D1

RvD4:

resolvin D4

References

  1. Keulenaer GWB DL (2008) Heart failure with preserved ejection fraction. Eur Cardiol 4(1):31–33

    Article  Google Scholar 

  2. Tannenbaum S, Sayer GT (2015) Advances in the pathophysiology and treatment of heart failure with preserved ejection fraction. Curr Opin Cardiol 30(3):250–258

    Article  PubMed  PubMed Central  Google Scholar 

  3. Halade GV, Kain V, Ingle KA (2018) Heart functional and structural compendium of cardiosplenic and cardiorenal networks in acute and chronic heart failure pathology. Am J Physiol Heart Circ Physiol 314(2):H255–Hh67

    Article  PubMed  CAS  Google Scholar 

  4. Westman PC, Lipinski MJ, Luger D, Waksman R, Bonow RO, Wu E et al (2016) Inflammation as a driver of adverse left ventricular remodeling after acute myocardial infarction. J Am Coll Cardiol 67(17):2050–2060

    Article  PubMed  Google Scholar 

  5. Duarte Vera YC, Caceres Vinueza SV, Daher Nader JE, Lara Teran JF (2018) A novel agent in the treatment of heart failure with depressed systolic function. Archivos de cardiologia de Mexico 88(4):287–297

    Article  PubMed  Google Scholar 

  6. Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M et al (2016) Executive summary: heart disease and stroke statistics--2016 update: a report from the American Heart Association. Circulation 133(4):447–454

    Article  PubMed  Google Scholar 

  7. Savarese G, Lund LH (2017) Global public health burden of heart failure. Card Fail Rev 3(1):7–11

    Article  PubMed  PubMed Central  Google Scholar 

  8. Halade GV, Kain V, Wright GM, Jadapalli JK (2018) Subacute treatment of carprofen facilitate splenocardiac resolution deficit in cardiac injury. J Leukoc Biol 104(6):1173–1186

    Article  CAS  PubMed  Google Scholar 

  9. Krishnan V, Booker D, Cunningham G, Jadapalli JK, Kain V, Pullen AB et al (2019) Pretreatment of carprofen impaired initiation of inflammatory- and overlapping resolution response and promoted cardiorenal syndrome in heart failure. Life Sci 218:224–232

    Article  CAS  PubMed  Google Scholar 

  10. McNeil JJ, Wolfe R, Woods RL, Tonkin AM, Donnan GA, Nelson MR et al (2018) Effect of aspirin on cardiovascular events and bleeding in the healthy elderly. N Engl J Med 379(16):1509–1518

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Banovic M, Pusnik-Vrckovnik M, Nakou E, Vardas P (2018) Myocardial regeneration therapy in heart failure: current status and future therapeutic implications in clinical practice. Int J Cardiol 260:124–130

    Article  PubMed  Google Scholar 

  12. Fredman G, Spite M (2017) Specialized pro-resolving mediators in cardiovascular diseases. Mol Asp Med 58:65–71

    Article  Google Scholar 

  13. Buckley CD, Gilroy DW, Serhan CN (2014) Proresolving lipid mediators and mechanisms in the resolution of acute inflammation. Immunity 40(3):315–327

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Kohli P, Levy BD (2009) Resolvins and protectins: mediating solutions to inflammation. Br J Pharmacol 158(4):960–971

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Sugimoto MA, Sousa LP, Pinho V, Perretti M, Teixeira MM (2016) Resolution of inflammation: what controls its onset? Front Immunol 7:160

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  16. Dick SA, Epelman S (2016) Chronic heart failure and inflammation: what do we really know? Circ Res 119(1):159–176

    Article  CAS  PubMed  Google Scholar 

  17. Jahng JW, Song E, Sweeney G (2016) Crosstalk between the heart and peripheral organs in heart failure. Exp Mol Med 48:e217

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Halade GV, Norris PC, Kain V, Serhan CN, Ingle KA (2018) Splenic leukocytes define the resolution of inflammation in heart failure. Sci Signal 11(520):eaao1818

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  19. Serhan CN (2014) Pro-resolving lipid mediators are leads for resolution physiology. Nature 510(7503):92–101

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Frangogiannis NG (2006) The mechanistic basis of infarct healing. Antioxid Redox Signal 8(11–12):1907–1939

    Article  CAS  PubMed  Google Scholar 

  21. Epelman S, Liu PP, Mann DL (2015) Role of innate and adaptive immune mechanisms in cardiac injury and repair. Nat Rev Immunol 15(2):117–129

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Zouggari Y, Ait-Oufella H, Bonnin P, Simon T, Sage AP, Guerin C et al (2013) B lymphocytes trigger monocyte mobilization and impair heart function after acute myocardial infarction. Nat Med 19(10):1273–1280

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Lai SL, Marin-Juez R, Stainier DYR (2018) Immune responses in cardiac repair and regeneration: a comparative point of view. Cell Mol Life Sci CMLS76(7):1365–1380

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  24. Shinde AV, Frangogiannis NG (2014) Fibroblasts in myocardial infarction: a role in inflammation and repair. J Mol Cell Cardiol 70:74–82

    Article  CAS  PubMed  Google Scholar 

  25. Aurora AB, Olson EN (2014) Immune modulation of stem cells and regeneration. Cell Stem Cell 15(1):14–25

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Madjid M, Fatemi O (2013) Components of the complete blood count as risk predictors for coronary heart disease: in-depth review and update. Tex Heart Inst J 40(1):17–29

    PubMed  PubMed Central  Google Scholar 

  27. Swirski FK, Nahrendorf M (2013) Leukocyte behavior in atherosclerosis, myocardial infarction, and heart failure. Science (New York, NY) 339(6116):161–166

    Article  CAS  Google Scholar 

  28. Aurora AB, Porrello ER, Tan W, Mahmoud AI, Hill JA, Bassel-Duby R et al (2014) Macrophages are required for neonatal heart regeneration. J Clin Invest 124(3):1382–1392

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Halade GV, Dorbane A, Ingle KA, Kain V, Schmitter JM, Rhourri-Frih B (2018) Comprehensive targeted and non-targeted lipidomics analyses in failing and non-failing heart. Anal Bioanal Chem 410(7):1965–1976

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Tourki B, Halade G (2017) Leukocyte diversity in resolving and nonresolving mechanisms of cardiac remodeling. FASEB J 31(10):4226–4239

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Jadapalli JK, Halade GV (2018) Unified nexus of macrophages and maresins in cardiac reparative mechanisms. FASEB J 32(10):5227–5237

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Frangogiannis NG (2014) The inflammatory response in myocardial injury, repair, and remodelling. Nat Rev Cardiol 11(5):255–265

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Frangogiannis NG (2012) Regulation of the inflammatory response in cardiac repair. Circ Res 110(1):159–173

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Robinette CD, Fraumeni JF Jr (1977) Splenectomy and subsequent mortality in veterans of the 1939-45 war. Lancet (London, UK) 2(8029):127–129

    Article  CAS  Google Scholar 

  35. Elajami TK, Colas RA, Dalli J, Chiang N, Serhan CN, Welty FK (2016) Specialized proresolving lipid mediators in patients with coronary artery disease and their potential for clot remodeling. FASEB J 30(8):2792–2801

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Serhan CN (2017) Treating inflammation and infection in the 21st century: new hints from decoding resolution mediators and mechanisms. FASEB J 31(4):1273–1288

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Frodermann V, Nahrendorf M (2017) Neutrophil-macrophage cross-talk in acute myocardial infarction. Eur Heart J 38(3):198–200

    CAS  PubMed  Google Scholar 

  38. Swirski FK (2015) Inflammation and repair in the ischaemic myocardium. Hamostaseologie 35(1):34–36

    Article  CAS  PubMed  Google Scholar 

  39. Horckmans M, Ring L, Duchene J, Santovito D, Schloss MJ, Drechsler M et al (2017) Neutrophils orchestrate post-myocardial infarction healing by polarizing macrophages towards a reparative phenotype. Eur Heart J 38(3):187–197

    CAS  PubMed  Google Scholar 

  40. Ma Y, Yabluchanskiy A, Iyer RP, Cannon PL, Flynn ER, Jung M et al (2016) Temporal neutrophil polarization following myocardial infarction. Cardiovasc Res 110(1):51–61

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Eming SA, Wynn TA, Martin P (2017) Inflammation and metabolism in tissue repair and regeneration. Science (New York, NY) 356(6342):1026–1030

    Article  CAS  Google Scholar 

  42. Heidt T, Courties G, Dutta P, Sager HB, Sebas M, Iwamoto Y et al (2014) Differential contribution of monocytes to heart macrophages in steady-state and after myocardial infarction. Circ Res 115(2):284–295

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Epelman S, Lavine KJ, Beaudin AE, Sojka DK, Carrero JA, Calderon B et al (2014) Embryonic and adult-derived resident cardiac macrophages are maintained through distinct mechanisms at steady state and during inflammation. Immunity 40(1):91–104

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Gombozhapova A, Rogovskaya Y, Shurupov V, Rebenkova M, Kzhyshkowska J, Popov SV et al (2017) Macrophage activation and polarization in post-infarction cardiac remodeling. J Biomed Sci 24(1):13

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  45. Weinberger T, Schulz C (2015) Myocardial infarction: a critical role of macrophages in cardiac remodeling. Front Physiol 6:107

    Article  PubMed  PubMed Central  Google Scholar 

  46. Yona S, Kim KW, Wolf Y, Mildner A, Varol D, Breker M et al (2013) Fate mapping reveals origins and dynamics of monocytes and tissue macrophages under homeostasis. Immunity 38(1):79–91

    Article  CAS  PubMed  Google Scholar 

  47. Linehan E, Fitzgerald DC (2015) Ageing and the immune system: focus on macrophages. Eu J Microbiol immunol 5(1):14–24

    Article  CAS  Google Scholar 

  48. Chen B, Frangogiannis NG (2016) Macrophages in the remodeling failing heart. Circ Res 119(7):776–778

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Frangogiannis NG (2015) Emerging roles for macrophages in cardiac injury: cytoprotection, repair, and regeneration. J Clin Invest 125(8):2927–2930

    Article  PubMed  PubMed Central  Google Scholar 

  50. Honold L, Nahrendorf M (2018) Resident and monocyte-derived macrophages in cardiovascular disease. Circ Res 122(1):113–127

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Lindsey ML, Saucerman JJ, DeLeon-Pennell KY (2016) Knowledge gaps to understanding cardiac macrophage polarization following myocardial infarction. Biochim Biophys Acta 1862(12):2288–2292

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Ma Y, Mouton AJ, Lindsey ML (2018) Cardiac macrophage biology in the steady-state heart, the aging heart, and following myocardial infarction. Trans Res J Lab Clin Med 191:15–28

    Google Scholar 

  53. Shiraishi M, Shintani Y, Shintani Y, Ishida H, Saba R, Yamaguchi A et al (2016) Alternatively activated macrophages determine repair of the infarcted adult murine heart. J Clin Invest 126(6):2151–2166

    Article  PubMed  PubMed Central  Google Scholar 

  54. Fraccarollo D, Galuppo P, Bauersachs J (2012) Novel therapeutic approaches to post-infarction remodelling. Cardiovasc Res 94(2):293–303

    Article  CAS  PubMed  Google Scholar 

  55. Ariel A, Serhan CN (2012) New lives given by cell death: macrophage differentiation following their encounter with apoptotic leukocytes during the resolution of inflammation. Front Immunol 3:4

    PubMed  PubMed Central  Google Scholar 

  56. Stables MJ, Shah S, Camon EB, Lovering RC, Newson J, Bystrom J et al (2011) Transcriptomic analyses of murine resolution-phase macrophages. Blood 118(26):e192–e208

    Article  CAS  PubMed  Google Scholar 

  57. Koh TJ, DiPietro LA (2011) Inflammation and wound healing: the role of the macrophage. Expert Rev Mol Med 13:e23

    Article  PubMed  PubMed Central  Google Scholar 

  58. Chiurchiu V, Leuti A, Dalli J, Jacobsson A, Battistini L, Maccarrone M et al (2016) Proresolving lipid mediators resolvin D1, resolvin D2, and maresin 1 are critical in modulating T cell responses. Sci Transl Med 8(353):353ra111

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  59. Halade GV, Black LM, Verma MK (2018) Paradigm shift – metabolic transformation of docosahexaenoic and eicosapentaenoic acids to bioactives exemplify the promise of fatty acid drug discovery. Biotechnol Adv 36(4):935–953

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Dalli J, Zhu M, Vlasenko NA, Deng B, Haeggstrom JZ, Petasis NA et al (2013) The novel 13S,14S-epoxy-maresin is converted by human macrophages to maresin 1 (MaR1), inhibits leukotriene A4 hydrolase (LTA4H), and shifts macrophage phenotype. FASEB J 27(7):2573–2583

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Dalli J, Serhan CN (2012) Specific lipid mediator signatures of human phagocytes: microparticles stimulate macrophage efferocytosis and pro-resolving mediators. Blood 120(15):e60–e72

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Sansbury BE, Spite M (2016) Resolution of acute inflammation and the role of Resolvins in immunity, thrombosis, and vascular biology. Circ Res 119(1):113–130

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Marcon R, Bento AF, Dutra RC, Bicca MA, Leite DF, Calixto JB (2013) Maresin 1, a proresolving lipid mediator derived from omega-3 polyunsaturated fatty acids, exerts protective actions in murine models of colitis. J Immunol 191(8):4288–4298

    Article  CAS  PubMed  Google Scholar 

  64. Lannan KL, Spinelli SL, Blumberg N, Phipps RP (2017) Maresin 1 induces a novel pro-resolving phenotype in human platelets. J Thromb haemost: JTH 15(4):802–813

    Article  CAS  PubMed  Google Scholar 

  65. Uderhardt S, Herrmann M, Oskolkova OV, Aschermann S, Bicker W, Ipseiz N et al (2012) 12/15-lipoxygenase orchestrates the clearance of apoptotic cells and maintains immunologic tolerance. Immunity 36(5):834–846

    Article  CAS  PubMed  Google Scholar 

  66. Kobayashi N, Karisola P, Pena-Cruz V, Dorfman DM, Jinushi M, Umetsu SE et al (2007) TIM-1 and TIM-4 glycoproteins bind phosphatidylserine and mediate uptake of apoptotic cells. Immunity 27(6):927–940

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Hellmann J, Tang Y, Kosuri M, Bhatnagar A, Spite M (2011) Resolvin D1 decreases adipose tissue macrophage accumulation and improves insulin sensitivity in obese-diabetic mice. FASEB J 25(7):2399–2407

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Titos E, Rius B, Gonzalez-Periz A, Lopez-Vicario C, Moran-Salvador E, Martinez-Clemente M et al (2011) Resolvin D1 and its precursor docosahexaenoic acid promote resolution of adipose tissue inflammation by eliciting macrophage polarization toward an M2-like phenotype. J Immunol 187(10):5408–5418

    Article  CAS  PubMed  Google Scholar 

  69. Cash JL, Norling LV, Perretti M (2014) Resolution of inflammation: targeting GPCRs that interact with lipids and peptides. Drug Discov Today 19(8):1186–1192

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Serhan CN, Hong S, Gronert K, Colgan SP, Devchand PR, Mirick G et al (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 

  71. Serhan CN, Hamberg M, Samuelsson B (1984) Lipoxins: novel series of biologically active compounds formed from arachidonic acid in human leukocytes. Proc Natl Acad Sci U S A 81(17):5335–5339

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Newson J, Stables M, Karra E, Arce-Vargas F, Quezada S, Motwani M et al (2014) Resolution of acute inflammation bridges the gap between innate and adaptive immunity. Blood 124(11):1748–1764

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. 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 

  74. Sansbury BE, Spite M (2016) Resolution of acute inflammation and the role of Resolvins in immunity, thrombosis, and vascular biology. Circ Res 119(1):113–130

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Kain V, Ingle KA, Colas RA, Dalli J, Prabhu SD, Serhan CN et al (2015) Resolvin D1 activates the inflammation resolving response at splenic and ventricular site following myocardial infarction leading to improved ventricular function. J Mol Cell Cardiol 84:24–35

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Serhan CN, Chiang N, Van Dyke TE (2008) Resolving inflammation: dual anti-inflammatory and pro-resolution lipid mediators. Nat Rev Immunol 8(5):349–361

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Colas RA, Souza PR, Walker ME, Burton M, Zaslona Z, Curtis AM et al (2018) Impaired production and diurnal regulation of vascular RvDn-3 DPA increase systemic inflammation and cardiovascular disease. Circ Res 122(6):855–863

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Serhan CN, Yacoubian S, Yang R (2008) Anti-inflammatory and proresolving lipid mediators. Annu Rev Pathol 3:279–312

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Hong S, Lu Y, Yang R, Gotlinger KH, Petasis NA, Serhan CN (2007) Resolvin D1, protectin D1, and related docosahexaenoic acid-derived products: analysis via electrospray/low energy tandem mass spectrometry based on spectra and fragmentation mechanisms. J Am Soc Mass Spectrom 18(1):128–144

    Article  CAS  PubMed  Google Scholar 

  80. Jadapalli JK, Halade GV (2018) Unified nexus of macrophages and maresins in cardiac reparative mechanisms. FASEB J 32(10):5227–5237

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Gilbert K, Bernier J, Bourque-Riel V, Malick M, Rousseau G (2015) Resolvin D1 reduces infarct size through a phosphoinositide 3-kinase/protein kinase B mechanism. J Cardiovasc Pharmacol 66(1):72–79

    Article  CAS  PubMed  Google Scholar 

  82. Gilbert K, Malick M, Madingou N, Bourque-Riel V, Touchette C, Rousseau G (2016) Linoleic acid attenuates cardioprotection induced by resolvin D1. J Nutr Biochem 31:122–126

    Article  CAS  PubMed  Google Scholar 

  83. Halade GV, Kain V, Serhan CN (2018) Immune responsive resolvin D1 programs myocardial infarction-induced cardiorenal syndrome in heart failure. FASEB J 32(7):3717–3729

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Zhang MJ, Sansbury BE, Hellmann J, Baker JF, Guo L, Parmer CM et al (2016) Resolvin D2 enhances Postischemic revascularization while resolving inflammation. Circulation 134(9):666–680

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Serhan CN, Petasis NA (2011) Resolvins and protectins in inflammation resolution. Chem Rev 111(10):5922–5943

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Varga Z, Sabzwari SRA, Vargova V (2017) Cardiovascular risk of nonsteroidal anti-inflammatory drugs: an under-recognized public health issue. Cureus 9(4):e1144

    PubMed  PubMed Central  Google Scholar 

  87. Cheng Y, Austin SC, Rocca B, Koller BH, Coffman TM, Grosser T et al (2002) Role of prostacyclin in the cardiovascular response to thromboxane A2. Science (New York, NY) 296(5567):539–541

    Article  CAS  Google Scholar 

  88. Fredman G, Ozcan L, Spolitu S, Hellmann J, Spite M, Backs J et al (2014) Resolvin D1 limits 5-lipoxygenase nuclear localization and leukotriene B4 synthesis by inhibiting a calcium-activated kinase pathway. Proc Natl Acad Sci USA 111(40):14530–14535

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Blomer N, Pachel C, Hofmann U, Nordbeck P, Bauer W, Mathes D et al (2013) 5-lipoxygenase facilitates healing after myocardial infarction. Basic Res Cardiol 108(4):367

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  90. Clària J, Dalli J, Yacoubian S, Gao F, Serhan CN (2012) Resolvin D1 and resolvin D2 govern local inflammatory tone in obese fat. J Immunol 189(5):2597–2605

    Article  PubMed  CAS  Google Scholar 

  91. Arnardottir HH, Dalli J, Colas RA, Shinohara M, Serhan CN (2014) Aging delays resolution of acute inflammation in mice: reprogramming the host response with novel nano-proresolving medicines. J Immunol 193(8):4235–4244

    Article  CAS  PubMed  Google Scholar 

  92. Arita M, Bianchini F, Aliberti J, Sher A, Chiang N, Hong S et al (2005) Stereochemical assignment, antiinflammatory properties, and receptor for the omega-3 lipid mediator resolvin E1. J Exp Med 201(5):713–722

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Arita M, Bianchini F, Aliberti J, Sher A, Chiang N, Hong S et al (2005) Stereochemical assignment, antiinflammatory properties, and receptor for the omega-3 lipid mediator resolvin E1. J Exp Med 201(5):713–722

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Schwab JM, Chiang N, Arita M, Serhan CN (2007) Resolvin E1 and protectin D1 activate inflammation-resolution programmes. Nature 447(7146):869–874

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Oh SF, Dona M, Fredman G, Krishnamoorthy S, Irimia D, Serhan CN (2012) Resolvin E2 formation and impact in inflammation resolution. J Immunol 188(9):4527–4534

    Article  CAS  PubMed  Google Scholar 

  96. Levy BD (2010) Resolvins and protectins: natural pharmacophores for resolution biology. Prostaglandins Leukot Essent Fatty Acids 82(4–6):327–332

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Chiang N, de la Rosa X, Libreros S, Serhan CN (2017) Novel Resolvin D2 receptor axis in infectious inflammation. J Immunol 198(2):842–851

    Article  CAS  PubMed  Google Scholar 

  98. Serhan CN (2007) Resolution phase of inflammation: novel endogenous anti-inflammatory and proresolving lipid mediators and pathways. Annu Rev Immunol 25:101–137

    Article  CAS  PubMed  Google Scholar 

  99. Samuelsson B, Hammarstrom S, Hamberg M, Serhan CN (1985) Structural determination of leukotrienes and lipoxins. Adv Prostaglandin Thromboxane Leukot Res 14:45–71

    CAS  PubMed  Google Scholar 

  100. Gronert K, Maheshwari N, Khan N, Hassan IR, Dunn M, Laniado Schwartzman M (2005) A role for the mouse 12/15-lipoxygenase pathway in promoting epithelial wound healing and host defense. J Biol Chem 280(15):15267–15278

    Article  CAS  PubMed  Google Scholar 

  101. Stables MJ, Gilroy DW (2011) Old and new generation lipid mediators in acute inflammation and resolution. Prog Lipid Res 50(1):35–51

    Article  CAS  PubMed  Google Scholar 

  102. Kain V, Liu F, Kozlovskaya V, Ingle KA, Bolisetty S, Agarwal A et al (2017) Resolution agonist 15-epi-Lipoxin A4 programs early activation of resolving phase in post-myocardial infarction healing. Sci Rep 7(1):9999

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  103. Kain V, Liu F, Kozlovskaya V, Ingle KA, Bolisetty S, Agarwal A et al (2017) Resolution agonist 15-epi-Lipoxin A4 programs early activation of resolving phase in post-myocardial infarction healing. Sci Rep 7(1):9999

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  104. Maderna P, Cottell DC, Toivonen T, Dufton N, Dalli J, Perretti M et al (2010) FPR2/ALX receptor expression and internalization are critical for lipoxin A4 and annexin-derived peptide-stimulated phagocytosis. FASEB J 24(11):4240–4249

    Article  CAS  PubMed  Google Scholar 

  105. Akagi D, Chen M, Toy R, Chatterjee A, Conte MS (2015) Systemic delivery of proresolving lipid mediators resolvin D2 and maresin 1 attenuates intimal hyperplasia in mice. FASEB J 29(6):2504–2513

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Serhan CN, Yang R, Martinod K, Kasuga K, Pillai PS, Porter TF et al (2009) Maresins: novel macrophage mediators with potent antiinflammatory and proresolving actions. J Exp Med 206(1):15–23

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Liu G, Liu Q, Shen Y, Kong D, Gong Y, Tao B et al (2018) Early treatment with Resolvin E1 facilitates myocardial recovery from ischaemia in mice. Br J Pharmacol 175(8):1205–1216

    Article  CAS  PubMed  Google Scholar 

  108. Colas RA, Dalli J, Chiang N, Vlasakov I, Sanger JM, Riley IR et al (2016) Identification and Actions of the Maresin 1 Metabolome in Infectious Inflammation. J Immunol 197(11):4444–4452

    Article  CAS  PubMed  Google Scholar 

  109. Viola JR, Lemnitzer P, Jansen Y, Csaba G, Winter C, Neideck C et al (2016) Resolving lipid mediators Maresin 1 and Resolvin D2 prevent Atheroprogression in mice. Circ Res 119(9):1030–1038

    Article  CAS  PubMed  Google Scholar 

  110. Tang S, Wan M, Huang W, Stanton RC, Xu Y (2018) Maresins: specialized Proresolving lipid mediators and their potential role in inflammatory-related diseases. Mediat Inflamm 2018:2380319

    Article  CAS  Google Scholar 

  111. Claria J, Lopez-Vicario C, Rius B, Titos E (2017) Pro-resolving actions of SPM in adipose tissue biology. Mol Asp Med 58:83–92

    Article  CAS  Google Scholar 

  112. Lee HN, Surh YJ (2013) Resolvin D1-mediated NOX2 inactivation rescues macrophages undertaking efferocytosis from oxidative stress-induced apoptosis. Biochem Pharmacol 86(6):759–769

    Article  CAS  PubMed  Google Scholar 

  113. Jove M, Mate I, Naudi A, Mota-Martorell N, Portero-Otin M, De la Fuente M et al (2016) Human aging is a metabolome-related matter of gender. J Gerontol A Biol Sci Med Sci 71(5):578–585

    Article  CAS  PubMed  Google Scholar 

  114. Dalli J, Serhan CN (2017) Pro-resolving mediators in regulating and conferring macrophage function. Front Immunol 8:1400

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  115. Ho KJ, Spite M, Owens CD, Lancero H, Kroemer AHK, Pande R et al (2010) Aspirin-triggered lipoxin and resolvin E1 modulate vascular smooth muscle phenotype and correlate with peripheral atherosclerosis. Am J Pathol 177(4):2116–2123

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Serhan CN, Takano T, Clish CB, Gronert K, Petasis N (1999) Aspirin-triggered 15-epi-lipoxin A4 and novel lipoxin B4 stable analogs inhibit neutrophil-mediated changes in vascular permeability. Adv Exp Med Biol 469:287–293

    Article  CAS  PubMed  Google Scholar 

  117. Lee CH (2012) Resolvins as new fascinating drug candidates for inflammatory diseases. Arch Pharm Res 35(1):3–7

    Article  CAS  PubMed  Google Scholar 

  118. Halade GV, Kain V, Wright GM, Jadeapalli JK (2018) Subacute treatment of carprofen facilitate splenocardiac resolution deficit in cardiac injury. J Leukoc Biol 104(6):1173–1186

    Article  CAS  PubMed  Google Scholar 

  119. Jadapalli JK, Wright GW, Kain V, Sherwani MA, Sonkar R, Yusuf N et al (2018) Doxorubicin triggers splenic contraction and irreversible dysregulation of COX and LOX that alters the inflammation-resolution program in the myocardium. Am J Physiol Heart Circ Physiol 315(5):H1091–Hh100

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Halade GV, Kain V (2017) Obesity and Cardiometabolic defects in heart failure pathology. Compr Physiol 7(4):1463–1477

    Article  PubMed  PubMed Central  Google Scholar 

  121. Tourki B, Halade GV (2018) The failing of the obesity paradox in the failing heart. Am J Physiol Heart Circ Physiol 315:H1353–H1355

    Article  CAS  PubMed Central  Google Scholar 

  122. Spite M, Clària J, Serhan CN (2014) Resolvins, specialized proresolving lipid mediators, and their potential roles in metabolic diseases. Cell Metab 19(1):21–36

    Article  CAS  PubMed  Google Scholar 

  123. Krishnamoorthy S, Recchiuti A, Chiang N, Yacoubian S, Lee C-H, Yang R et al (2010) Resolvin D1 binds human phagocytes with evidence for proresolving receptors. Proc Natl Acad Sci U S A 107(4):1660–1665

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Lopez EF, Kabarowski JH, Ingle KA, Kain V, Barnes S, Crossman DK et al (2015) Obesity superimposed on aging magnifies inflammation and delays the resolving response after myocardial infarction. Am J Physiol Heart Circ Physiol 308(4):H269–H280

    Article  CAS  PubMed  Google Scholar 

  125. Martín-Timón I, Sevillano-Collantes C, Segura-Galindo A, Del Cañizo-Gómez FJ (2014) Type 2 diabetes and cardiovascular disease: have all risk factors the same strength? World J Diabetes 5(4):444–470

    Article  PubMed  PubMed Central  Google Scholar 

  126. Freire MO, Dalli J, Serhan CN, Van Dyke TE (2017) Neutrophil Resolvin E1 receptor expression and function in type 2 diabetes. J Immunol 198(2):718–728

    Article  CAS  PubMed  Google Scholar 

  127. Ferrante AW Jr (2007) Obesity-induced inflammation: a metabolic dialogue in the language of inflammation. J Intern Med 262(4):408–414

    Article  CAS  PubMed  Google Scholar 

  128. Ouchi N, Parker JL, Lugus JJ, Walsh K (2011) Adipokines in inflammation and metabolic disease. Nat Rev Immunol 11(2):85–97

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Hotamisligil GS (2006) Inflammation and metabolic disorders. Nature 444(7121):860–867

    Article  CAS  PubMed  Google Scholar 

  130. Hellmann J, Tang Y, Kosuri M, Bhatnagar A, Spite M (2011) Resolvin D1 decreases adipose tissue macrophage accumulation and improves insulin sensitivity in obese-diabetic mice. FASEB J 25(7):2399–2407

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Titos E, Rius B, González-Périz A, López-Vicario C, Morán-Salvador E, Martínez-Clemente M et al (2011) Resolvin D1 and its precursor docosahexaenoic acid promote resolution of adipose tissue inflammation by eliciting macrophage polarization toward an M2-like phenotype. J Immunol 187(10):5408–5418

    Article  CAS  PubMed  Google Scholar 

  132. Brennan EP, Mohan M, McClelland A, de Gaetano M, Tikellis C, Marai M et al (2018) Lipoxins protect against inflammation in diabetes-associated atherosclerosis. Diabetes 67(12):2657–2667

    Article  PubMed  Google Scholar 

  133. Tang Y, Zhang MJ, Hellmann J, Kosuri M, Bhatnagar A, Spite M (2013) Proresolution therapy for the treatment of delayed healing of diabetic wounds. Diabetes 62(2):618–627

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Kannan A, Janardhanan R (2014) Hypertension as a risk factor for heart failure. Curr Hypertens Rep 16(7):447

    Article  PubMed  CAS  Google Scholar 

  135. Pearson T, Zhang J, Arya P, Warren AY, Ortori C, Fakis A et al (2010) Measurement of vasoactive metabolites (hydroxyeicosatetraenoic and epoxyeicosatrienoic acids) in uterine tissues of normal and compromised human pregnancy. J Hypertens 28(12):2429–2437

    CAS  PubMed  Google Scholar 

  136. Didion SP (2017) Unraveling the role and complexities of inflammation in hypertension, Hypertension (Dallas, Tex: 1979). 70(4):700–702

    Google Scholar 

  137. Pullamsetti SS, Savai R, Janssen W, Dahal BK, Seeger W, Grimminger F et al (2011) Inflammation, immunological reaction and role of infection in pulmonary hypertension. Clin Microbiol Infect 17(1):7–14

    Article  CAS  PubMed  Google Scholar 

  138. Hiram R, Rizcallah E, Sirois C, Sirois M, Morin C, Fortin S et al (2014) Resolvin D1 reverses reactivity and Ca2+ sensitivity induced by ET-1, TNF-alpha, and IL-6 in the human pulmonary artery. Am J Physiol Heart Circ Physiol 307(11):H1547–H1558

    Article  CAS  PubMed  Google Scholar 

  139. McAlpine CS, Swirski FK (2016) Circadian influence on metabolism and inflammation in atherosclerosis. Circ Res 119(1):131–141

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  140. Perretti M, D’Acquisto F (2009) Annexin A1 and glucocorticoids as effectors of the resolution of inflammation. Nat Rev Immunol 9(1):62–70

    Article  CAS  PubMed  Google Scholar 

  141. 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 

  142. 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  143. Young ME, Brewer RA, Peliciari-Garcia RA, Collins HE, He L, Birky TL et al (2014) Cardiomyocyte-specific BMAL1 plays critical roles in metabolism, signaling, and maintenance of contractile function of the heart. J Biol Rhythm 29(4):257–276

    Article  CAS  Google Scholar 

  144. Colas RA, Souza PR, Walker ME, Burton M, Zasłona Z, Curtis AM et al (2018) Impaired production and diurnal regulation of vascular RvDn-3 DPA increase systemic inflammation and cardiovascular disease. Circ Res 122(6):855–863

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  145. Alvarez P, Hannawi B, Guha A (2016) Exercise and heart failure: advancing knowledge and improving care. Methodist Debakey Cardiovasc J 12(2):110–115

    Article  PubMed  PubMed Central  Google Scholar 

  146. Markworth JF, Vella L, Lingard BS, Tull DL, Rupasinghe TW, Sinclair AJ et al (2013) Human inflammatory and resolving lipid mediator responses to resistance exercise and ibuprofen treatment. Am J Physiol Regul Integr Comp Physiol 305(11):R1281–R1296

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  147. Gangemi S, Pescara L, D’Urbano E, Basile G, Nicita-Mauro V, Davì G et al (2005) Aging is characterized by a profound reduction in anti-inflammatory lipoxin A4 levels. Exp Gerontol 40(7):612–614

    Article  CAS  PubMed  Google Scholar 

  148. Taylor RS, Sagar VA, Davies EJ, Briscoe S, Coats AJ, Dalal H et al (2014) Exercise-based rehabilitation for heart failure. Cochrane Database Syst Rev (4):Cd003331

    Google Scholar 

  149. Hoetker D, Chung W, Zhang D, Zhao J, Schmidtke VK, Riggs DW et al (2018) Exercise alters and beta-alanine combined with exercise augments histidyl dipeptide levels and scavenges lipid peroxidation products in human skeletal muscle. J Appl Physiol (1985). https://doi.org/10.1152/japplphysiol.00007.2018

    Article  CAS  Google Scholar 

  150. Meschiari CA, Ero OK, Pan H, Finkel T, Lindsey ML (2017) The impact of aging on cardiac extracellular matrix. GeroScience 39(1):7–18

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  151. Franceschi C, Campisi J (2014) Chronic inflammation (inflammaging) and its potential contribution to age-associated diseases. J Gerontol A Biol Sci Med Sci 69(Suppl 1):S4–S9

    Article  PubMed  Google Scholar 

  152. Yabluchanskiy A, Ma Y, DeLeon-Pennell KY, Altara R, Halade GV, Voorhees AP et al (2016) Myocardial infarction superimposed on aging: MMP-9 deletion promotes M2 macrophage polarization. J Gerontol A Biol Sci Med Sci 71(4):475–483

    Article  CAS  PubMed  Google Scholar 

  153. Yabluchanskiy A, Ma Y, Chiao YA, Lopez EF, Voorhees AP, Toba H et al (2014) Cardiac aging is initiated by matrix metalloproteinase-9-mediated endothelial dysfunction. Am J Physiol Heart Circ Physiol 306(10):H1398–H1407

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  154. Melton DW, Roberts AC, Wang H, Sarwar Z, Wetzel MD, Wells JT et al (2016) Absence of CCR2 results in an inflammaging environment in young mice with age-independent impairments in muscle regeneration. J Leukoc Biol 100(5):1011–1025

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  155. Halade GV, Kain V, Black LM, Prabhu SD, Ingle KA (2016) Aging dysregulates D- and E-series resolvins to modulate cardiosplenic and cardiorenal network following myocardial infarction. Aging 8(11):2611–2634

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  156. Jové M, Maté I, Naudí A, Mota-Martorell N, Portero-Otín M, De la Fuente M et al (2016) Human aging is a metabolome-related matter of gender. J Gerontol A Biol Sci Med Sci 71(5):578–585

    Article  PubMed  CAS  Google Scholar 

  157. Buford TW. (Dis)Trust your gut: the gut microbiome in age-related inflammation, health, and disease. Microbiome. 2017;5(\):80

    Article  PubMed  PubMed Central  Google Scholar 

  158. Zabell A, Tang WHW (2017) Targeting the microbiome in heart failure. Curr Treat Options Cardiovasc Med 19(4):27

    Article  PubMed  Google Scholar 

  159. Luedde M, Winkler T, Heinsen F-A, Rühlemann MC, Spehlmann ME, Bajrovic A et al (2017) Heart failure is associated with depletion of core intestinal microbiota. ESC Heart Fail 4(3):282–290

    Article  PubMed  PubMed Central  Google Scholar 

  160. Menni C, Zierer J, Pallister T, Jackson MA, Long T, Mohney RP et al (2017) Omega-3 fatty acids correlate with gut microbiome diversity and production of N-carbamylglutamate in middle aged and elderly women. Sci Rep 7(1):11079

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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Acknowledgements

Authors acknowledge the support from National Institutes of Health (NIH)-NCCIH (formerly known as NCCAM) AT006704, HL132989 and UAB Pittman Scholar Award to GVH. The authors would like to thank Servier Medical Art images bank that used to create the illustrations in Figs. 6.1, 6.2 and 6.3.

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  1. Department of Medicine, Division of Cardiovascular Disease, The University of Alabama at Birmingham, Birmingham, AL, USA

    Ganesh V. Halade & Bochra Tourki

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  1. Ganesh V. Halade
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Correspondence to Ganesh V. Halade .

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

    Kenneth V. Honn

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

    Darryl C. Zeldin

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Halade, G.V., Tourki, B. (2019). Specialized Pro-resolving Mediators Directs Cardiac Healing and Repair with Activation of Inflammation and Resolution Program in Heart Failure. 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_6

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