[go: up one dir, main page]
More Web Proxy on the site http://driver.im/ Skip to main content

Advertisement

Log in

The leukotriene receptor antagonist montelukast and its possible role in the cardiovascular field

  • Review
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Background

Cysteinyl leukotrienes (LTC4, LTD4, and LTE4) are pro-inflammatory mediators of the 5-lipooxygenase (5-LO) pathway, that play an important role in bronchoconstriction, but can also enhance endothelial cell permeability and myocardial contractility, and are involved in many other inflammatory conditions. In the late 1990s, leukotriene receptor antagonists (LTRAs) were introduced in therapy for asthma and later on, approved for the relief of the symptoms of allergic rhinitis, chronic obstructive pulmonary disease, and urticaria. In addition, it has been shown that LTRAs may have a potential role in preventing atherosclerosis progression.

Purpose

The aims of this short review are to delineate the potential cardiovascular protective role of a LTRA, montelukast, beyond its traditional use, and to foster the design of appropriate clinical trials to test this hypothesis.

Results and Conclusions

What it is known about leukotriene receptor antagonists?

•Leukotriene receptor antagonist, such as montelukast and zafirlukast, is used in asthma, COPD, and allergic rhinitis.

• Montelukast is the most prescribed CysLT1 antagonist used in asthmatic patients.

• Different in vivo animal studies have shown that leukotriene receptor antagonists can prevent the atherosclerosis progression, and have a protective role after cerebral ischemia.

What we still need to know?

• Today, there is a need for conducting clinical trials to assess the role of montelukast in reducing cardiovascular risk and to further understand the mechanism of action behind this effect.

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

Access this article

Subscribe and save

Springer+ Basic
£29.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (United Kingdom)

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  1. Marnett LJ, Rowlinson SW, Goodwin DC, Kalgutkar AS, Lanzo CA (1999) Arachidonic acid oxigenation by COX-1 and COX-2. J Biol Chem 274:22903–22906

    Article  CAS  PubMed  Google Scholar 

  2. Funk CD, Funk LB, Kennedy ME, Pong AS, Fitzgerald GA (1991) Human platelet/erythroleukemia cell prostaglandin G/H synthase: cDNA cloning, expression, and gene chromosomal assignment. FASEB J 5(9):2304–2312

    CAS  PubMed  Google Scholar 

  3. Takahashi Y, Ueda N, Yoshimoto T, Yamamoto S, Yokoyama C, Miyata A, Tanabe T, Fuse I, Hattori A, Shibata A (1992) Immunoaffinity purification and cDNA cloning of human platelet prostaglandin endoperoxide synthase (cyclooxygenase). Biochem Biophys Res Commun 182(2):433–438

    Article  CAS  PubMed  Google Scholar 

  4. Smith WL, DeWitt DL, Garavito RM (2000) Cyclooxygenases: structural, cellular, and molecular biology. Annu Rev Biochem 69:145–182

    Article  CAS  PubMed  Google Scholar 

  5. Haeggstrom JZ, Funk CD (2011) Lipoxygenase and leukotriene pathways: biochemistry, biology, and roles in disease. Chem Rev 111(10):5866–5898

    Article  PubMed  CAS  Google Scholar 

  6. Yokomizo T, Izumi T, Shimizu T (2001) Leukotriene B4: metabolism and signal transduction. Arch Biochem Biophys 385(2):231–241

    Article  CAS  PubMed  Google Scholar 

  7. Back M, Dahlen SE, Drazen JM, Evans JF, Serhan CN, Shimizu T, Yokomizo T, Rovati GE (2011) International Union of Basic and Clinical Pharmacology. LXXXIV: leukotriene receptor nomenclature, distribution, and pathophysiological functions. Pharmacol Rev 63(3):539–584

    Article  PubMed  CAS  Google Scholar 

  8. Back M, Powell WS, Dahlen SE, Drazen JM, Evans JF, Serhan CN, Shimizu T, Yokomizo T, Rovati GE (2014) International Union of Basic and Clinical Pharmacology. Update on leukotriene, lipoxin and oxoeicosanoid receptors: IUPHAR review 7. Br J Pharmacol 171(15):3551–3574

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  9. Capra V (2004) Molecular and functional aspects of human cysteinyl leukotriene receptors. Pharmacol Res 50(1):1–11

    Article  CAS  PubMed  Google Scholar 

  10. Kanaoka Y, Boyce JA (2004) Cysteinyl leukotrienes and their receptors: cellular distribution and function in immune and inflammatory responses. J Immunol 173(3):1503–1510

    Article  CAS  PubMed  Google Scholar 

  11. Capra V, Thompson MD, Sala A, Cole DE, Folco G, Rovati GE (2007) Cysteinyl-leukotrienes and their receptors in asthma and other inflammatory diseases: critical update and emerging trends. Med Res Rev 27(4):469–527

    Article  CAS  PubMed  Google Scholar 

  12. Nicosia S, Capra V, Rovati GE (2001) Leukotrienes as mediators of asthma. Pulm Pharmacol Ther 14(1):3–19

    Article  CAS  PubMed  Google Scholar 

  13. Lotzer K, Funk CD, Habenicht AJ (2005) The 5-lipoxygenase pathway in arterial wall biology and atherosclerosis. Biochim Biophys Acta 1736(1):30–37

    PubMed  Google Scholar 

  14. Riccioni G, Capra V, D'Orazio N, Bucciarelli T, Bazzano LA (2008) Leukotriene modifiers in the treatment of cardiovascular diseases. J Leukoc Biol 84(6):1374–1378

    Article  CAS  PubMed  Google Scholar 

  15. Bäck M (2009) Leukotriene signaling in atherosclerosis and ischemia. Cardiovasc Drugs Ther 23(1):41–48

    Article  PubMed  CAS  Google Scholar 

  16. Riccioni G, Bäck M, Capra V (2010) Leukotrienes and atherosclerosis. Curr Drug Targets 11(7):882–887

    Article  CAS  PubMed  Google Scholar 

  17. Bäck M (2007) Leukotriene receptors: crucial components in vascular inflammation. ScientificWorldJournal 7:1422–1439

    Article  PubMed  CAS  Google Scholar 

  18. Michelassi F, Landa L, Hill RD, Lowenstein E, Watkins WD, Petkau AJ, Zapol WM (1982) Leukotriene D4: a potent coronary artery vasoconstrictor associated with impaired ventricular contraction. Science 217(4562):841–843

    Article  CAS  PubMed  Google Scholar 

  19. Porreca E, Di Febbo C, Di Sciullo A, Angelucci D, Nasuti M, Vitullo P, Reale M, Conti P, Cuccurullo F, Poggi A (1996) Cysteinyl leukotriene D4 induced vascular smooth muscle cell proliferation: a possible role in myointimal hyperplasia. Thromb Haemost 76(1):99–104

    CAS  PubMed  Google Scholar 

  20. McIntyre TM, Zimmerman GA, Prescott SM (1986) Leukotrienes C4 and D4 stimulate human endothelial cells to synthesize platelet-activating factor and bind neutrophils. Proc Natl Acad Sci U S A 83(7):2204–2208

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Datta YH, Romano M, Jacobson BC, Golan DE, Serhan CN, Ewenstein BM (1995) Peptido-leukotrienes are potent agonists of von Willebrand factor secretion and P-selectin surface expression in human umbilical vein endothelial cells. Circulation 92(11):3304–3311

    Article  CAS  PubMed  Google Scholar 

  22. Pedersen KE, Bochner BS, Undem BJ (1997) Cysteinyl leukotrienes induce P-selectin expression in human endothelial cells via a non-CysLT1 receptor-mediated mechanism. Journal of Pharmacology & Experimental Therapeutics 281(2):655–662

    CAS  Google Scholar 

  23. Carry M, Korley V, Willerson JT, Weigelt L, Ford-Hutchinson AW, Tagari P (1992) Increased urinary leukotriene excretion in patients with cardiac ischemia. In vivo evidence for 5-lipoxygenase activation. Circulation 85(1):230–236

    Article  CAS  PubMed  Google Scholar 

  24. De Caterina R, Giannessi D, Lazzerini G, Bernini W, Sicari R, Cupelli F, Lenzi S, Rugolotto MM, Madonna R, Maclouf J (2010) Sulfido-peptide leukotrienes in coronary heart disease—relationship with disease instability and myocardial ischaemia. Eur J Clin Investig 40(3):258–272

    Article  CAS  Google Scholar 

  25. Allen SP, Sampson AP, Piper PJ, Chester AH, Ohri SK, Yacoub MH (1993) Enhanced excretion of urinary leukotriene E4 in coronary artery disease and after coronary artery bypass surgery. Coron Artery Dis 4(10):899–904

    Article  CAS  PubMed  Google Scholar 

  26. Sala A, Rossoni G, Berti F, Buccellati C, Bonazzi A, Maclouf J, Folco G (2000) Monoclonal anti-CD18 antibody prevents transcellular biosynthesis of cysteinyl leukotrienes in vitro and in vivo and protects against leukotriene-dependent increase in coronary vascular resistance and myocardial stiffness. Circulation 101(12):1436–1440

    Article  CAS  PubMed  Google Scholar 

  27. Sala A, Rossoni G, Buccellati C, Berti F, Folco G, Maclouf J (1993) Formation of sulphidopeptide-leukotrienes by cell-cell interaction causes coronary vasoconstriction in isolated, cell-perfused heart of rabbit. Br J Pharmacol 110(3):1206–1212

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Rossoni G, Sala A, Berti F, Testa T, Buccellati C, Molta C, Muller-Peddinghaus R, Maclouf J, Folco GC (1996) Myocardial protection by the leukotriene synthesis inhibitor BAY X1005: importance of transcellular biosynthesis of cysteinyl-leukotrienes. J Pharmacol Exp Ther 276(1):335–341

    CAS  PubMed  Google Scholar 

  29. Dwyer JH, Allayee H, Dwyer KM, Fan J, Wu H, Mar R, Lusis AJ, Mehrabian M (2004) Arachidonate 5-lipoxygenase promoter genotype, dietary arachidonic acid, and atherosclerosis. N Engl J Med 350(1):29–37

    Article  CAS  PubMed  Google Scholar 

  30. Helgadottir A, Manolescu A, Thorleifsson G, Gretarsdottir S, Jonsdottir H, Thorsteinsdottir U, Samani NJ, Gudmundsson G, Grant SF, Thorgeirsson G, Sveinbjornsdottir S, Valdimarsson EM, Matthiasson SE, Johannsson H, Gudmundsdottir O, Gurney ME, Sainz J, Thorhallsdottir M, Andresdottir M, Frigge ML, Topol EJ, Kong A, Gudnason V, Hakonarson H, Gulcher JR, Stefansson K (2004) The gene encoding 5-lipoxygenase activating protein confers risk of myocardial infarction and stroke. Nat Genet 36(3):233–239

    Article  CAS  PubMed  Google Scholar 

  31. Maekawa A, Austen KF, Kanaoka Y (2002) Targeted gene disruption reveals the role of cysteinyl leukotriene 1 receptor in the enhanced vascular permeability of mice undergoing acute inflammatory responses. J Biol Chem 277(23):20820–20824

    Article  CAS  PubMed  Google Scholar 

  32. Spanbroek R, Grabner R, Lotzer K, Hildner M, Urbach A, Ruhling K, Moos MP, Kaiser B, Cohnert TU, Wahlers T, Zieske A, Plenz G, Robenek H, Salbach P, Kuhn H, Radmark O, Samuelsson B, Habenicht AJ (2003) Expanding expression of the 5-lipoxygenase pathway within the arterial wall during human atherogenesis. Proc Natl Acad Sci U S A 100(3):1238–1243

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Nagy E, Andersson DC, Caidahl K, Eriksson MJ, Eriksson P, Franco-Cereceda A, Hansson GK, Back M (2011) Upregulation of the 5-lipoxygenase pathway in human aortic valves correlates with severity of stenosis and leads to leukotriene-induced effects on valvular myofibroblasts. Circulation 123(12):1316–1325

    Article  CAS  PubMed  Google Scholar 

  34. Eaton A, Nagy E, Pacault M, Fauconnier J, Back M (2012) Cysteinyl leukotriene signaling through perinuclear CysLT(1) receptors on vascular smooth muscle cells transduces nuclear calcium signaling and alterations of gene expression. J Mol Med (Berl) 90(10):1223–1231

    Article  CAS  Google Scholar 

  35. Minamisawa H, Terashi A, Katayama Y, Kanda Y, Shimizu J, Shiratori T, Inamura K, Kaseki H, Yoshino Y (1988) Brain eicosanoid levels in spontaneously hypertensive rats after ischemia with reperfusion: leukotriene C4 as a possible cause of cerebral edema. Stroke 19(3):372–377

    Article  CAS  PubMed  Google Scholar 

  36. Ciceri P, Rabuffetti M, Monopoli A, Nicosia S (2001) Production of leukotrienes in a model of focal cerebral ischaemia in the rat. Br J Pharmacol 133(8):1323–1329

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Di Gennaro A, Carnini C, Buccellati C, Ballerio R, Zarini S, Fumagalli F, Viappiani S, Librizzi L, Hernandez A, Murphy RC, Constantin G, De Curtis M, Folco G, Sala A (2004) Cysteinyl-leukotrienes receptor activation in brain inflammatory reactions and cerebral edema formation: a role for transcellular biosynthesis of cysteinyl-leukotrienes. FASEB J 18(7):842–844

    CAS  PubMed  Google Scholar 

  38. Sheng WW, Li CT, Zhang WP, Yuan YM, Hu H, Fang SH, Zhang L, Wei EQ (2006) Distinct roles of CysLT1 and CysLT2 receptors in oxygen glucose deprivation-induced PC12 cell death. Biochem Biophys Res Commun 346(1):19–25

    Article  CAS  PubMed  Google Scholar 

  39. Wang ML, Huang XJ, Fang SH, Yuan YM, Zhang WP, Lu YB, Ding Q, Wei EQ (2006) Leukotriene D4 induces brain edema and enhances CysLT2 receptor-mediated aquaporin 4 expression. Biochem Biophys Res Commun 350(2):399–404

    Article  CAS  PubMed  Google Scholar 

  40. Huang XJ, Zhang WP, Li CT, Shi WZ, Fang SH, Lu YB, Chen Z, Wei EQ (2008) Activation of CysLT receptors induces astrocyte proliferation and death after oxygen-glucose deprivation. Glia 56(1):27–37

    Article  PubMed  Google Scholar 

  41. Letts LG (1987) Leukotrienes: role in cardiovascular physiology. Cardiovasc Clin 18(1):101–113

    CAS  PubMed  Google Scholar 

  42. Folco G, Rossoni G, Buccellati C, Berti F, Maclouf J, Sala A (2000) Leukotrienes in cardiovascular diseases. Am J Respir Crit Care Med 161(2 Pt 2):S112–S116

    Article  CAS  PubMed  Google Scholar 

  43. Back M (2009) Inhibitors of the 5-lipoxygenase pathway in atherosclerosis. Curr Pharm Des 15(27):3116–3132

    Article  PubMed  Google Scholar 

  44. Poeckel D, Funk CD (2010) The 5-lipoxygenase/leukotriene pathway in preclinical models of cardiovascular disease. Cardiovasc Res 86(2):243–253

  45. Capra V, Back M, Barbieri SS, Camera M, Tremoli E, Rovati GE (2013) Eicosanoids and their drugs in cardiovascular diseases: focus on atherosclerosis and stroke. Med Res Rev 33(2):364–438

    Article  CAS  PubMed  Google Scholar 

  46. Griffin M, Weiss JW, Leitch AG, McFadden ER Jr, Corey EJ, Austen KF, Drazen JM (1983) Effects of leukotriene D on the airways in asthma. N Engl J Med 308(8):436–439

    Article  CAS  PubMed  Google Scholar 

  47. Dahlen SE, Hansson G, Hedqvist P, Björck T, Granström E, Dahlen B (1983) Allergen challenge of lung tissue from asthmatics elicits bronchial contraction that correlates with the release of leukotrienes C4, D4 and E4. Proc Natl Acad Sci U S A 80:1712–1716

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Lewis RA, Robin JL (1985) Arachidonic acid derivatives as mediators of asthma. J Allergy Clin Immunol 76:259–264

    Article  CAS  PubMed  Google Scholar 

  49. Adelroth E, Morris MM, Hargreave FE, O'Byrne PM (1986) Airway responsiveness to leukotrienes C4 and D4 and to methacholine in patients with asthma and normal controls. N Engl J Med 315(8):480–484

    Article  CAS  PubMed  Google Scholar 

  50. Davidson AB, Lee TH, Scanlon PD, Solway J, McFadden ER Jr, Ingram RH Jr, Corey EJ, Austen KF, Drazen JM (1987) Bronchoconstrictor effects of leukotriene E4 in normal and asthmatic subjects. Am Rev Respir Dis 135(2):333–337

    CAS  PubMed  Google Scholar 

  51. Israel E, Dermarkarian R, Rosenberg M, Sperling R, Taylor G, Rubin P, Drazen JM (1990) The effects of a 5-lipoxygenase inhibitor on asthma induced by cold, dry air. N Engl J Med 323(25):1740–1744

    Article  CAS  PubMed  Google Scholar 

  52. O'Byrne PM, Israel E, Drazen JM (1997) Antileukotrienes in the treatment of asthma. Ann Intern Med 127(6):472–480

    Article  PubMed  Google Scholar 

  53. Claesson HE, Dahlen SE (1999) Asthma and leukotrienes: antileukotrienes as novel anti-asthmatic drugs. J Intern Med 245(3):205–227

    Article  CAS  PubMed  Google Scholar 

  54. Lipworth BJ (1999) Leukotriene-receptor antagonists. Lancet 353(9146):57–62

    Article  CAS  PubMed  Google Scholar 

  55. Salvi SS, Krishna MT, Sampson AP, Holgate ST (2001) The anti-inflammatory effects of leukotriene-modifying drugs and their use in asthma. Chest 119(5):1533–1546

    Article  CAS  PubMed  Google Scholar 

  56. Currie GP, Lipworth BJ (2002) Bronchoprotective effects of leukotriene receptor antagonists in asthma: a meta-analysis. Chest 122(1):146–150

    Article  PubMed  Google Scholar 

  57. Capra V, Rovati GE (2004) Leukotriene modifiers in asthma management. IDrugs 7(7):659–666

    CAS  PubMed  Google Scholar 

  58. Capra V, Ambrosio M, Riccioni G, Rovati GE (2006) Cysteinyl-leukotriene receptor antagonists: present situation and future opportunities. Curr Med Chem 13(26):3213–3226

    Article  CAS  PubMed  Google Scholar 

  59. Capra V, Carnini C, Accomazzo MR, Di Gennaro A, Fiumicelli M, Borroni E, Brivio I, Buccellati C, Mangano P, Carnevali S, Rovati G, Sala A (2015) Autocrine activity of cysteinyl leukotrienes in human vascular endothelial cells: signaling through the CysLT receptor. Prostaglandins Other Lipid Mediat 120:115–125

    Article  CAS  PubMed  Google Scholar 

  60. Labat C, Ortiz JL, Norel X, Gorenne I, Verley J, Abram TS, Cuthbert NJ, Tudhope SR, Norman P, Gardiner P et al (1992) A second cysteinyl leukotriene receptor in human lung. J Pharmacol Exp Ther 263(2):800–805

    CAS  PubMed  Google Scholar 

  61. Tudhope SR, Cuthbert NJ, Abram TS, Jennings MA, Maxey RJ, Thompson AM, Norman P, Gardiner PJ (1994) BAY u9773, a novel antagonist of cysteinil-leukotrienes with activity against two receptor subtypes. Eur J Pharmacol 264:317–323

    Article  CAS  PubMed  Google Scholar 

  62. Carnini C, Accomazzo MR, Borroni E, Vitellaro-Zuccarello L, Durand T, Folco G, Rovati GE, Capra V, Sala A (2011) Synthesis of cysteinyl leukotrienes in human endothelial cells: subcellular localization and autocrine signaling through the CysLT2 receptor. FASEB J 25(10):3519–3528

    Article  CAS  PubMed  Google Scholar 

  63. Ni NC, Yan D, Ballantyne LL, Barajas-Espinosa A, St Amand T, Pratt DA, Funk CD (2011) A selective cysteinyl leukotriene receptor 2 antagonist blocks myocardial ischemia/reperfusion injury and vascular permeability in mice. J Pharmacol Exp Ther 339(3):768–778

    Article  CAS  PubMed  Google Scholar 

  64. Wunder F, Tinel H, Kast R, Geerts A, Becker EM, Kolkhof P, Hutter J, Erguden J, Harter M (2010) Pharmacological characterization of the first potent and selective antagonist at the cysteinyl leukotriene 2 (CysLT(2)) receptor. Br J Pharmacol 160(2):399–409

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Drazen JM, Israel E, O'Byrne PM (1999) Treatment of asthma with drugs modifying the leukotriene pathway. N Engl J Med 340(3):197–206

    Article  CAS  PubMed  Google Scholar 

  66. Sasaki K, Ueno A, Kawamura M, Katori M, Shigehiro S, Kikawada R (1987) Reduction of myocardial infarct size in rats by a selective 5-lipoxygenase inhibitor (AA-861). Adv Prostaglandin Thromboxane Leukot Res 17A:381–383

    CAS  PubMed  Google Scholar 

  67. Hashimoto H, Miyazawa K, Hagiwara M, Miyasaka K, Nakashima M (1990) Beneficial effects of a new 5-lipoxygenase inhibitor on occlusion- and occlusion-reperfusion-induced myocardial injury. Arzneimittelforschung 40(2 Pt 1):126–129

    CAS  PubMed  Google Scholar 

  68. Welt K, Fitzl G, Mark B (2000) Lipoxygenase inhibitor FLM 5011, an effective protectant of myocardial microvessels against ischemia-reperfusion injury? An ultrastructural-morphometric study. Exp Toxicol Pathol 52(1):27–36

    Article  CAS  PubMed  Google Scholar 

  69. Jawien J, Gajda M, Rudling M, Mateuszuk L, Olszanecki R, Guzik TJ, Cichocki T, Chlopicki S, Korbut R (2006) Inhibition of five lipoxygenase activating protein (FLAP) by MK-886 decreases atherosclerosis in apoE/LDLR-double knockout mice. Eur J Clin Investig 36(3):141–146

    Article  CAS  Google Scholar 

  70. Bäck M, Sultan A, Ovchinnikova O, Hansson GK (2007) 5-Lipoxygenase-activating protein: a potential link between innate and adaptive immunity in atherosclerosis and adipose tissue inflammation. Circ Res 100(7):946–949

    Article  PubMed  CAS  Google Scholar 

  71. Amsterdam EA, Pan HL, Rendig SV, Symons JD, Fletcher MP, Longhurst JC (1993) Limitation of myocardial infarct size in pigs with a dual lipoxygenase-cyclooxygenase blocking agent by inhibition of neutrophil activity without reduction of neutrophil migration. J Am Coll Cardiol 22(6):1738–1744

    Article  CAS  PubMed  Google Scholar 

  72. Vidal C, Gomez-Hernandez A, Sanchez-Galan E, Gonzalez A, Ortega L, Gomez-Gerique JA, Tunon J, Egido J (2007) Licofelone, a balanced inhibitor of cyclooxygenase and 5-lipoxygenase, reduces inflammation in a rabbit model of atherosclerosis. J Pharmacol Exp Ther 320(1):108–116

    Article  CAS  PubMed  Google Scholar 

  73. Mullane K, Hatala MA, Kraemer R, Sessa W, Westlin W (1987) Myocardial salvage induced by REV-5901: an inhibitor and antagonist of the leukotrienes. J Cardiovasc Pharmacol 10(4):398–406

    Article  CAS  PubMed  Google Scholar 

  74. Hahn RA, MacDonald BR, Simpson PJ, Wang L, Towner RD, Ho PP, Goodwin M, Breau AP, Suarez T, Mihelich ED (1991) Characterization of LY233569 on 5-lipoxygenase and reperfusion injury of ischemic myocardium. J Pharmacol Exp Ther 256(1):94–102

    CAS  PubMed  Google Scholar 

  75. Adamek A, Jung S, Dienesch C, Laser M, Ertl G, Bauersachs J, Frantz S (2007) Role of 5-lipoxygenase in myocardial ischemia-reperfusion injury in mice. Eur J Pharmacol 571(1):51–54

    Article  CAS  PubMed  Google Scholar 

  76. Zhao L, Moos MP, Grabner R, Pedrono F, Fan J, Kaiser B, John N, Schmidt S, Spanbroek R, Lotzer K, Huang L, Cui J, Rader DJ, Evans JF, Habenicht AJ, Funk CD (2004) The 5-lipoxygenase pathway promotes pathogenesis of hyperlipidemia-dependent aortic aneurysm. Nat Med 10(9):966–973

    Article  CAS  PubMed  Google Scholar 

  77. Cao RY, St Amand T, Grabner R, Habenicht AJ, Funk CD (2009) Genetic and pharmacological inhibition of the 5-lipoxygenase/leukotriene pathway in atherosclerotic lesion development in ApoE deficient mice. Atherosclerosis 203(2):395–400

    Article  CAS  PubMed  Google Scholar 

  78. Whatling C, McPheat W, Herslof M (2007) The potential link between atherosclerosis and the 5-lipoxygenase pathway: investigational agents with new implications for the cardiovascular field. Expert Opin Investig Drugs 16(12):1879–1893

    Article  CAS  PubMed  Google Scholar 

  79. Hakonarson H, Thorvaldsson S, Helgadottir A, Gudbjartsson D, Zink F, Andresdottir M, Manolescu A, Arnar DO, Andersen K, Sigurdsson A, Thorgeirsson G, Jonsson A, Agnarsson U, Bjornsdottir H, Gottskalksson G, Einarsson A, Gudmundsdottir H, Adalsteinsdottir AE, Gudmundsson K, Kristjansson K, Hardarson T, Kristinsson A, Topol EJ, Gulcher J, Kong A, Gurney M, Thorgeirsson G, Stefansson K (2005) Effects of a 5-lipoxygenase-activating protein inhibitor on biomarkers associated with risk of myocardial infarction: a randomized trial. JAMA 293(18):2245–2256

    Article  CAS  PubMed  Google Scholar 

  80. Tardif JC, L'Allier PL, Ibrahim R, Gregoire JC, Nozza A, Cossette M, Kouz S, Lavoie MA, Paquin J, Brotz TM, Taub R, Pressacco J (2010) Treatment with 5-lipoxygenase inhibitor VIA-2291 (atreleuton) in patients with recent acute coronary syndrome. Circ Cardiovasc Imaging 3(3):298–307

    Article  PubMed  Google Scholar 

  81. Matsumoto S , Ibrahim R , Grégoire JC , L'Allier PL , Pressacco J , Tardif J-C and Budoff MJ (2016) Effect of treatment with 5-lipoxygenase inhibitor VIA-2291 (atreleuton) on coronary plaque progression: a serial CT angiography study. Clin Cardiol. doi:10.1002/clc.22646

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Serhan CN (2017) Treating inflammation and infection in the 21st century: new hints from decoding resolution mediators and mechanisms. FASEB J. doi:10.1096/fj.201601222R

  84. Fredman G, Spite M (2017) Specialized pro-resolving mediators in cardiovascular diseases. Mol Aspects Med pii: S0098–2997(17)30017–1. doi:10.1016/j.mam.2017.02.003

  85. Hecht I, Rong J, Sampaio AL, Hermesh C, Rutledge C, Shemesh R, Toporik A, Beiman M, Dassa L, Niv H, Cojocaru G, Zauberman A, Rotman G, Perretti M, Vinten-Johansen J, Cohen Y (2009) A novel peptide agonist of formyl-peptide receptor-like 1 (ALX) displays anti-inflammatory and cardioprotective effects. J Pharmacol Exp Ther 328(2):426–434

    Article  CAS  PubMed  Google Scholar 

  86. Fierro IM, Kutok JL, Serhan CN (2002) Novel lipid mediator regulators of endothelial cell proliferation and migration: aspirin-triggered-15R-lipoxin A(4) and lipoxin A(4). J Pharmacol Exp Ther 300(2):385–392

    Article  CAS  PubMed  Google Scholar 

  87. Nascimento-Silva V, Arruda MA, Barja-Fidalgo C, Villela CG, Fierro IM (2005) Novel lipid mediator aspirin-triggered lipoxin A4 induces heme oxygenase-1 in endothelial cells. Am J Physiol 289(3):C557–C563

    Article  CAS  Google Scholar 

  88. Nascimento-Silva V, Arruda MA, Barja-Fidalgo C, Fierro IM (2007) Aspirin-triggered lipoxin A4 blocks reactive oxygen species generation in endothelial cells: a novel antioxidative mechanism. Thromb Haemost 97(1):88–98

    CAS  PubMed  Google Scholar 

  89. Fredman G, Van Dyke TE, Serhan CN (2010) Resolvin E1 regulates adenosine diphosphate activation of human platelets. Arterioscler Thromb Vasc Biol 30(10):2005–2013

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Yedgar S, Krimsky M, Cohen Y, Flower RJ (2007) Treatment of inflammatory diseases by selective eicosanoid inhibition: a double-edged sword? Trends Pharmacol Sci 28(9):459–464

    Article  CAS  PubMed  Google Scholar 

  91. Lipworth BJ (2001) Emerging role of antileukotriene therapy in allergic rhinitis. Clin Exp Allergy 31(12):1813–1821

    Article  CAS  PubMed  Google Scholar 

  92. Nayak AS, Philip G, Lu S, Malice MP, Reiss TF (2002) Efficacy and tolerability of montelukast alone or in combination with loratadine in seasonal allergic rhinitis: a multicenter, randomized, double-blind, placebo-controlled trial performed in the fall. Ann Allergy Asthma Immunol 88(6):592–600

    Article  CAS  PubMed  Google Scholar 

  93. Meltzer EO, Malmstrom K, Lu S, Prenner BM, Wei LX, Weinstein SF, Wolfe JD, Reiss TF (2000) Concomitant montelukast and loratadine as treatment for seasonal allergic rhinitis: a randomized, placebo-controlled clinical trial. J Allergy Clin Immunol 105(5):917–922

    Article  CAS  PubMed  Google Scholar 

  94. Adachi M, Taniguchi H, Tohda Y, Sano Y, Ishine T, Smugar SS, Hisada S (2012) The efficacy and tolerability of intravenous montelukast in acute asthma exacerbations in Japanese patients. J Asthma 49(6):649–656

    Article  CAS  PubMed  Google Scholar 

  95. Reiss TF, Sorkness CA, Stricker W, Botto A, Busse WW, Kundu S, Zhang J (1997) Effects of montelukast (MK-0476); a potent cysteinyl leukotriene receptor antagonist, on bronchodilation in asthmatic subjects treated with and without inhaled corticosteroids. Thorax 52(1):45–48

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Noonan MJ, Chervinsky P, Brandon M, Zhang J, Kundu S, McBurney J, Reiss TF (1998) Montelukast, a potent leukotriene receptor antagonist, causes dose-related improvements in chronic asthma. Montelukast Asthma Study Group. Eur Respir J 11(6):1232–1239

    Article  CAS  PubMed  Google Scholar 

  97. Dockhorn RJ, Baumgartner RA, Leff JA, Noonan M, Vandormael K, Stricker W, Weinland DE, Reiss TF (2000) Comparison of the effects of intravenous and oral montelukast on airway function: a double blind, placebo controlled, three period, crossover study in asthmatic patients. Thorax 55(4):260–265

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Rubinstein I, Kumar B, Schriever C (2004) Long-term montelukast therapy in moderate to severe COPD—a preliminary observation. Respir Med 98(2):134–138

    Article  PubMed  Google Scholar 

  99. Celik P, Sakar A, Havlucu Y, Yuksel H, Turkdogan P, Yorgancioglu A (2005) Short-term effects of montelukast in stable patients with moderate to severe COPD. Respir Med 99(4):444–450

    Article  PubMed  Google Scholar 

  100. Miligkos M, Bannuru RR, Alkofide H, Kher SR, Schmid CH, Balk EM (2015) Leukotriene-receptor antagonists versus placebo in the treatment of asthma in adults and adolescents: a systematic review and meta-analysis. Ann Intern Med 163(10):756–767

    Article  PubMed  PubMed Central  Google Scholar 

  101. Price D, Musgrave SD, Shepstone L, Hillyer EV, Sims EJ, Gilbert RF, Juniper EF, Ayres JG, Kemp L, Blyth A, Wilson EC, Wolfe S, Freeman D, Mugford HM, Murdoch J, Harvey I (2011) Leukotriene antagonists as first-line or add-on asthma-controller therapy. N Engl J Med 364(18):1695–1707

    Article  CAS  PubMed  Google Scholar 

  102. Chauhan BF, Ducharme FM (2012) Anti-leukotriene agents compared to inhaled corticosteroids in the management of recurrent and/or chronic asthma in adults and children. Cochrane database of systematic reviews (Online) 5:CD002314

    Google Scholar 

  103. Knorr B, Matz J, Bernstein JA, Nguyen H, Seidenberg BC, Reiss TF, Becker A (1998) Montelukast for chronic asthma in 6- to 14-year-old children: a randomized, double-blind trial. Pediatric Montelukast study Group. JAMA 279(15):1181–1186

    Article  CAS  PubMed  Google Scholar 

  104. Bisgaard H, Skoner D, Boza ML, Tozzi CA, Newcomb K, Reiss TF, Knorr B, Noonan G (2009) Safety and tolerability of montelukast in placebo-controlled pediatric studies and their open-label extensions. Pediatr Pulmonol 44(6):568–579

    Article  PubMed  Google Scholar 

  105. Berube D, Djandji M, Sampalis JS, Becker A (2014) Effectiveness of montelukast administered as monotherapy or in combination with inhaled corticosteroid in pediatric patients with uncontrolled asthma: a prospective cohort study. Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology 10(1):21

    Article  CAS  Google Scholar 

  106. Schmitt-Grohe S, Eickmeier O, Schubert R, Bez C, Zielen S (2002) Anti-inflammatory effects of montelukast in mild cystic fibrosis. Ann Allergy Asthma Immunol 89(6):599–605

    Article  CAS  PubMed  Google Scholar 

  107. Stelmach I, Korzeniewska A, Stelmach W, Majak P, Grzelewski T, Jerzynska J (2005) Effects of montelukast treatment on clinical and inflammatory variables in patients with cystic fibrosis. Ann Allergy Asthma Immunol 95(4):372–380

    Article  CAS  PubMed  Google Scholar 

  108. Fitzgerald DA, Mellis CM (2006) Leukotriene receptor antagonists in virus-induced wheezing: evidence to date. Treat Respir Med 5(6):407–417

    Article  CAS  PubMed  Google Scholar 

  109. Sener G, Sehirli O, Cetinel S, Ercan F, Yuksel M, Gedik N, Yegen BC (2005) Amelioration of sepsis-induced hepatic and ileal injury in rats by the leukotriene receptor blocker montelukast. Prostaglandins Leukot Essent Fatty Acids 73(6):453–462

    Article  CAS  PubMed  Google Scholar 

  110. Maeba S, Ichiyama T, Ueno Y, Makata H, Matsubara T, Furukawa S (2005) Effect of montelukast on nuclear factor kappaB activation and proinflammatory molecules. Ann Allergy Asthma Immunol 94(6):670–674

    Article  CAS  PubMed  Google Scholar 

  111. Wu Y, Zhou C, Tao J, Li S (2006) Montelukast prevents the decrease of interleukin-10 and inhibits NF-kappaB activation in inflammatory airway of asthmatic guinea pigs. Can J Physiol Pharmacol 84(5):531–537

    Article  CAS  PubMed  Google Scholar 

  112. Tahan F, Jazrawi E, Moodley T, Rovati GE, Adcock IM (2008) Montelukast inhibits tumour necrosis factor-alpha-mediated interleukin-8 expression through inhibition of nuclear factor-kappaB p65-associated histone acetyltransferase activity. Clin Exp Allergy 38(5):805–811

    Article  CAS  PubMed  Google Scholar 

  113. Chiba M, Xu X, Nishime JA, Balani SK, Lin JH (1997) Hepatic microsomal metabolism of montelukast, a potent leukotriene D4 receptor antagonist, in humans. Drug metabolism and disposition: the biological fate of chemicals 25(9):1022–1031

    CAS  Google Scholar 

  114. Bush A (2015) Montelukast in paediatric asthma: where we are now and what still needs to be done? Paediatr Respir Rev 16(2):97–100

    PubMed  Google Scholar 

  115. Price D (2000) Tolerability of montelukast. Drugs 59(Suppl 1):35–42 discussion 43-35

    Article  CAS  PubMed  Google Scholar 

  116. Garcia-Marcos L, Schuster A, Perez-Yarza EG (2003) Benefit-risk assessment of antileukotrienes in the management of asthma. Drug Saf 26(7):483–518

    Article  CAS  PubMed  Google Scholar 

  117. Virchow JC, Bachert C (2006) Efficacy and safety of montelukast in adults with asthma and allergic rhinitis. Respir Med 100(11):1952–1959

    Article  PubMed  Google Scholar 

  118. Paggiaro P, Bacci E (2011) Montelukast in asthma: a review of its efficacy and place in therapy. Ther Adv Chronic Dis 2(1):47–58

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Biber N, Toklu HZ, Solakoglu S, Gultomruk M, Hakan T, Berkman Z, Dulger FG (2009) Cysteinyl-leukotriene receptor antagonist montelukast decreases blood-brain barrier permeability but does not prevent oedema formation in traumatic brain injury. Brain Inj 23(6):577–584

    Article  PubMed  Google Scholar 

  120. Yu GL, Wei EQ, Zhang SH, Xu HM, Chu LS, Zhang WP, Zhang Q, Chen Z, Mei RH, Zhao MH (2005) Montelukast, a cysteinyl leukotriene receptor-1 antagonist, dose- and time-dependently protects against focal cerebral ischemia in mice. Pharmacology 73(1):31–40

    Article  CAS  PubMed  Google Scholar 

  121. Yu GL, Wei EQ, Wang ML, Zhang WP, Zhang SH, Weng JQ, Chu LS, Fang SH, Zhou Y, Chen Z, Zhang Q, Zhang LH (2005) Pranlukast, a cysteinyl leukotriene receptor-1 antagonist, protects against chronic ischemic brain injury and inhibits the glial scar formation in mice. Brain Res 1053(1–2):116–125

    Article  CAS  PubMed  Google Scholar 

  122. Qian XD, Wei EQ, Zhang L, Sheng WW, Wang ML, Zhang WP, Chen Z (2006) Pranlukast, a cysteinyl leukotriene receptor 1 antagonist, protects mice against brain cold injury. Eur J Pharmacol 549(1–3):35–40

    Article  CAS  PubMed  Google Scholar 

  123. Fang SH, Wei EQ, Zhou Y, Wang ML, Zhang WP, Yu GL, Chu LS, Chen Z (2006) Increased expression of cysteinyl leukotriene receptor-1 in the brain mediates neuronal damage and astrogliosis after focal cerebral ischemia in rats. Neuroscience 140(3):969–979

    Article  CAS  PubMed  Google Scholar 

  124. Zhao R, Shi WZ, Zhang YM, Fang SH, Wei EQ (2011) Montelukast, a cysteinyl leukotriene receptor-1 antagonist, attenuates chronic brain injury after focal cerebral ischaemia in mice and rats. J Pharm Pharmacol 63(4):550–557

    Article  CAS  PubMed  Google Scholar 

  125. Huang XQ, Zhang XY, Wang XR, Yu SY, Fang SH, Lu YB, Zhang WP, Wei EQ (2012) Transforming growth factor beta1-induced astrocyte migration is mediated in part by activating 5-lipoxygenase and cysteinyl leukotriene receptor 1. J Neuroinflammation 9:145

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Saad MA, Abdelsalam RM, Kenawy SA, Attia AS (2015) Montelukast, a cysteinyl leukotriene receptor-1 antagonist protects against hippocampal injury induced by transient global cerebral ischemia and reperfusion in rats. Neurochem Res 40(1):139–150

    Article  CAS  PubMed  Google Scholar 

  127. Cavus G, Altas M, Aras M, Ozgur T, Serarslan Y, Yilmaz N, Sefil F, Ulutas KT (2014) Effects of montelukast and methylprednisolone on experimental spinal cord injury in rats. Eur Rev Med Pharmacol Sci 18(12):1770–1777

    CAS  PubMed  Google Scholar 

  128. Fang SH, Zhou Y, Chu LS, Zhang WP, Wang ML, Yu GL, Peng F, Wei EQ (2007) Spatio-temporal expression of cysteinyl leukotriene receptor-2 mRNA in rat brain after focal cerebral ischemia. Neurosci Lett 412(1):78–83

    Article  CAS  PubMed  Google Scholar 

  129. Qi LL, Fang SH, Shi WZ, Huang XQ, Zhang XY, Lu YB, Zhang WP, Wei EQ (2011) CysLT2 receptor-mediated AQP4 up-regulation is involved in ischemic-like injury through activation of ERK and p38 MAPK in rat astrocytes. Life Sci 88(1–2):50–56

    Article  CAS  PubMed  Google Scholar 

  130. Zhao CZ, Zhao B, Zhang XY, Huang XQ, Shi WZ, Liu HL, Fang SH, Lu YB, Zhang WP, Tang FD, Wei EQ (2011) Cysteinyl leukotriene receptor 2 is spatiotemporally involved in neuron injury, astrocytosis and microgliosis after focal cerebral ischemia in rats. Neuroscience 189:1–11

    Article  CAS  PubMed  Google Scholar 

  131. Shi QJ, Xiao L, Zhao B, Zhang XY, Wang XR, Xu DM, Yu SY, Fang SH, Lu YB, Zhang WP, Sa XY, Wei EQ (2012) Intracerebroventricular injection of HAMI 3379, a selective cysteinyl leukotriene receptor 2 antagonist, protects against acute brain injury after focal cerebral ischemia in rats. Brain Res 1484:57–67

    Article  CAS  PubMed  Google Scholar 

  132. Shi QJ, Wang H, Liu ZX, Fang SH, Song XM, Lu YB, Zhang WP, Sa XY, Ying HZ, Wei EQ (2015) HAMI 3379, a CysLT2R antagonist, dose- and time-dependently attenuates brain injury and inhibits microglial inflammation after focal cerebral ischemia in rats. Neuroscience 291:53–69

    Article  CAS  PubMed  Google Scholar 

  133. Zhang XY, Wang XR, Xu DM, Yu SY, Shi QJ, Zhang LH, Chen L, Fang SH, Lu YB, Zhang WP, Wei EQ (2013) HAMI 3379, a CysLT2 receptor antagonist, attenuates ischemia-like neuronal injury by inhibiting microglial activation. J Pharmacol Exp Ther 346(2):328–341

    Article  CAS  PubMed  Google Scholar 

  134. Kaetsu Y, Yamamoto Y, Sugihara S, Matsuura T, Igawa G, Matsubara K, Igawa O, Shigemasa C, Hisatome I (2007) Role of cysteinyl leukotrienes in the proliferation and the migration of murine vascular smooth muscle cells in vivo and in vitro. Cardiovasc Res 76(1):160–166

    Article  CAS  PubMed  Google Scholar 

  135. Jawien J, Gajda M, Wolkow P, Zuranska J, Olszanecki R, Korbut R (2008) The effect of montelukast on atherogenesis in apoE/LDLR-double knockout mice. J Physiol Pharmacol 59(3):633–639

    CAS  PubMed  Google Scholar 

  136. Mueller CF, Wassmann K, Widder JD, Wassmann S, Chen CH, Keuler B, Kudin A, Kunz WS, Nickenig G (2008) Multidrug resistance protein-1 affects oxidative stress, endothelial dysfunction, and atherogenesis via leukotriene C4 export. Circulation 117(22):2912–2918

    Article  CAS  PubMed  Google Scholar 

  137. Liu D, Ge S, Zhou G, Xu G, Zhang R, Zhu W, Liu Z, Cheng S, Liu X (2009) Montelukast inhibits matrix metalloproteinases expression in atherosclerotic rabbits. Cardiovasc Drugs Ther 23(6):431–437

    Article  CAS  PubMed  Google Scholar 

  138. Ge S, Zhou G, Cheng S, Liu D, Xu J, Xu G, Liu X (2009) Anti-atherogenic effects of montelukast associated with reduced MCP-1 expression in a rabbit carotid balloon injury model. Atherosclerosis 205(1):74–79

    Article  CAS  PubMed  Google Scholar 

  139. Becher UM, Ghanem A, Tiyerili V, Furst DO, Nickenig G, Mueller CF (2011) Inhibition of leukotriene C4 action reduces oxidative stress and apoptosis in cardiomyocytes and impedes remodeling after myocardial injury. J Mol Cell Cardiol 50(3):570–577

    Article  CAS  PubMed  Google Scholar 

  140. Nobili E, Salvado MD, Folkersen L, Castiglioni L, Kastrup J, Wetterholm A, Tremoli E, Hansson GK, Sironi L, Haeggstrom JZ, Gabrielsen A (2012) Cysteinyl leukotriene signaling aggravates myocardial hypoxia in experimental atherosclerotic heart disease. PLoS One 7(7):e41786

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  141. Daglar G, Karaca T, Yuksek YN, Gozalan U, Akbiyik F, Sokmensuer C, Gurel B, Kama NA (2009) Effect of montelukast and MK-886 on hepatic ischemia-reperfusion injury in rats. J Surg Res 153(1):31–38

    Article  CAS  PubMed  Google Scholar 

  142. Duran A, Otiuk H, Terzi EH, Tosun M, Oziiu H, Ocak T, Kiiuer A (2013) Protective effect of montelukast, a cysteinyl leukotriene receptor-1 antagonist, against intestinal ischemia-reperfusion injury in the rat. Acta Chir Belg 113(6):401–405

    CAS  PubMed  Google Scholar 

  143. Wu S, Zhu X, Jin Z, Tong X, Zhu L, Hong X, Zhu X, Liu P, Shen W (2015) The protective role of montelukast against intestinal ischemia-reperfusion injury in rats. Scientific reports 5:15787

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  144. Ozkan E, Yardimci S, Dulundu E, Topaloglu U, Sehirli O, Ercan F, Velioglu-Ogunc A, Sener G (2010) Protective potential of montelukast against hepatic ischemia/reperfusion injury in rats. J Surg Res 159(1):588–594

    Article  PubMed  CAS  Google Scholar 

  145. Celik A, Ergun E, Koksal N, Celik AS, Altinli E, Uzun MA, Eroglu E, Kemik A (2013) Effects of montelukast on the healing of ischemic colon anastomoses. Am J Surg 206(4):502–508

    Article  CAS  PubMed  Google Scholar 

  146. Oral A, Odabasoglu F, Halici Z, Keles ON, Unal B, Coskun AK, Kilic C, Surer I, Salman AB (2011) Protective effects of montelukast on ischemia-reperfusion injury in rat ovaries subjected to torsion and detorsion: biochemical and histopathologic evaluation. Fertil Steril 95(4):1360–1366

    Article  CAS  PubMed  Google Scholar 

  147. Akdemir A, Erbas O, Ergenoglu M, Ozgur Yeniel A, Oltulu F, Yavasoglu A, Taskiran D (2014) Montelukast prevents ischaemia/reperfusion-induced ovarian damage in rats. Eur J Obstet Gynecol Reprod Biol 173:71–76

    Article  CAS  PubMed  Google Scholar 

  148. Ozturk H, Ozturk H, Gideroglu K, Terzi H, Bugdayci G (2010) Montelukast protects against testes ischemia/reperfusion injury in rats. Can Urol Assoc J 4(3):174–179

    Article  PubMed  PubMed Central  Google Scholar 

  149. Sener G, Sehirli O, Velioglu-Ogunc A, Cetinel S, Gedik N, Caner M, Sakarcan A, Yegen BC (2006) Montelukast protects against renal ischemia/reperfusion injury in rats. Pharmacol Res 54(1):65–71

    Article  CAS  PubMed  Google Scholar 

  150. Sener G, Sehirli O, Toklu H, Ercan F, Alican I (2007) Montelukast reduces ischaemia/reperfusion-induced bladder dysfunction and oxidant damage in the rat. J Pharm Pharmacol 59(6):837–842

    Article  CAS  PubMed  Google Scholar 

  151. Muthuraman A, Ramesh M, Sood S (2012) Ameliorative potential of montelukast on ischemia-reperfusion injury induced vasculitic neuropathic pain in rat. Life Sci 90(19–20):755–762

    Article  CAS  PubMed  Google Scholar 

  152. Lafci G, Gedik HS, Korkmaz K, Erdem H, Cicek OF, Nacar OA, Yildirim L, Kaya E, Ankarali H (2013) Efficacy of iloprost and montelukast combination on spinal cord ischemia/reperfusion injury in a rat model. J Cardiothorac Surg 8:64

    Article  PubMed  PubMed Central  Google Scholar 

  153. Hagar HH, Abd El Tawab R (2012) Cysteinyl leukotriene receptor antagonism alleviates renal injury induced by ischemia-reperfusion in rats. J Surg Res 178(1):e25–e34

    Article  CAS  PubMed  Google Scholar 

  154. Kezeli T, Gongadze N, Chapichadze Z, Bakuridze K, Chirakadze K (2010) Effect of combination of zafirlukast and quercetin on baroreflex sensitivity and endothelin production in rats with myocardial infarction. Int J Clin Pharmacol Ther 48(5):335–341

    Article  CAS  PubMed  Google Scholar 

  155. DeClue AE, Sharp CR, Cohen RL, Leverenz EF, Reinero CR (2010) Cysteinyl-leukotriene receptor antagonism blunts the acute hypotensive response to endotoxin in cats. J Feline Med Surg 12(10):754–759

    Article  PubMed  Google Scholar 

  156. Toki Y, Hieda N, Torii T, Hashimoto H, Ito T, Ogawa K, Satake T (1988) The effects of lipoxygenase inhibitor and peptidoleukotriene antagonist on myocardial injury in a canine coronary occlusion-reperfusion model. Prostaglandins 35(4):555–571

    Article  CAS  PubMed  Google Scholar 

  157. Zhao R, Fang SH, Lin KN, Huang XQ, Lu YB, Zhang WP, Wei EQ (2011) Pranlukast attenuates hydrogen peroxide-induced necrosis in endothelial cells by inhibiting oxygen reactive species-mediated collapse of mitochondrial membrane potential. J Cardiovasc Pharmacol 57(4):479–488

    Article  CAS  PubMed  Google Scholar 

  158. Fang SH, Yuan YM, Peng F, Li CT, Zhang LH, Lu YB, Zhang WP, Wei EQ (2009) Pranlukast attenuates ischemia-like injury in endothelial cells via inhibiting reactive oxygen species production and nuclear factor-kappaB activation. J Cardiovasc Pharmacol 53(1):77–85

    Article  CAS  PubMed  Google Scholar 

  159. Allayee H, Hartiala J, Lee W, Mehrabian M, Irvin CG, Conti DV, Lima JJ (2007) The effect of montelukast and low-dose theophylline on cardiovascular disease risk factors in asthmatics. Chest 132(3):868–874

    Article  CAS  PubMed  Google Scholar 

  160. Ingelsson E, Yin L, Bäck M (2012) Nationwide cohort study of the leukotriene receptor antagonist montelukast and incident or recurrent cardiovascular disease. J Allergy Clin Immunol 129(3):702–707

  161. Duah E, Adapala RK, Al-Azzam N, Kondeti V, Gombedza F, Thodeti CK, Paruchuri S (2013) Cysteinyl leukotrienes regulate endothelial cell inflammatory and proliferative signals through CysLT(2) and CysLT(1) receptors. Scientific reports 3:3274

    Article  PubMed  PubMed Central  Google Scholar 

  162. Porreca E, Di Febbo C, Reale M, Barbacane R, Mezzetti A, Cuccurullo F, Conti P (1995) Modulation of rat vascular smooth muscle cell (VSMC) proliferation by cysteinyl leukotriene D4: a role for mediation of interleukin 1. Atherosclerosis 113(1):11–18

    Article  CAS  PubMed  Google Scholar 

  163. Bousquet J, Demoly P, Humbert M (2009) Montelukast in guidelines and beyond. Adv Ther 26(6):575–587

    Article  PubMed  Google Scholar 

  164. Funk CD (2005) Leukotriene modifiers as potential therapeutics for cardiovascular disease. Nat Rev Drug Discov 4(8):664–672

    Article  CAS  PubMed  Google Scholar 

  165. Iribarren C, Tolstykh IV, Miller MK, Sobel E, Eisner MD (2012) Adult asthma and risk of coronary heart disease, cerebrovascular disease, and heart failure: a prospective study of 2 matched cohorts. Am J Epidemiol 176(11):1014–1024

    Article  PubMed  Google Scholar 

  166. Amlani S, Nadarajah T, McIvor RA (2011) Montelukast for the treatment of asthma in the adult population. Expert Opin Pharmacother 12(13):2119–2128

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Malvina Hoxha.

Electronic supplementary material

ESM 1

(DOCX 28 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hoxha, M., Rovati, G.E. & Cavanillas, A.B. The leukotriene receptor antagonist montelukast and its possible role in the cardiovascular field. Eur J Clin Pharmacol 73, 799–809 (2017). https://doi.org/10.1007/s00228-017-2242-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00228-017-2242-2

Keywords

Navigation