{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T08:19:38Z","timestamp":1791361178110,"version":"4.3.1"},"reference-count":115,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2022,9,14]],"date-time":"2022-09-14T00:00:00Z","timestamp":1663113600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the French Agence Nationale de la Recherche","award":["2020 07132"],"award-info":[{"award-number":["2020 07132"]}]},{"name":"the R\u00e9gion Pays de la Loire","award":["2020 07132"],"award-info":[{"award-number":["2020 07132"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Acute coronary syndrome (ACS) is a set of signs and symptoms caused by a reduction of coronary blood flow with subsequent myocardial ischemia. ACS is associated with activation of the leukotriene (LT) pathway with subsequent releases of various LTs, including LTB4, LTC4, and LTD4, which cause inflammatory changes and induction of immunothrombosis. LTs through cysteine leukotriene (CysLT) induce activation of platelets and clotting factors with succeeding coronary thrombosis. CysLT receptor (CysLTR) antagonists such as montelukast (MK) may reduce the risk of the development of ACS and associated complications through suppression of the activation of platelet and clotting factors. Thus, this critical review aimed to elucidate the possible protective role of MK in the management of ACS. The LT pathway is implicated in the pathogenesis of atherosclerosis, cardiac hypertrophy, and heart failure. Inhibition of the LT pathway and CysL1TR by MK might be effective in preventing cardiovascular complications. MK could be an effective novel therapy in the management of ACS through inhibition of pro-inflammatory CysLT1R and modulation of inflammatory signaling pathways. MK can attenuate thrombotic events by inhibiting platelet activation and clotting factors that are activated during the development of ACS. In conclusion, MK could be an effective agent in reducing the severity of ACS and associated complications. Experimental, preclinical, and clinical studies are recommended to confirm the potential therapeutic of MK in the management of ACS.<\/jats:p>","DOI":"10.3390\/ph15091147","type":"journal-article","created":{"date-parts":[[2022,9,14]],"date-time":"2022-09-14T23:16:36Z","timestamp":1663197396000},"page":"1147","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Montelukast and Acute Coronary Syndrome: The Endowed Drug"],"prefix":"10.3390","volume":"15","author":[{"given":"Basil Mohammed","family":"Alomair","sequence":"first","affiliation":[{"name":"Internal Medicine, Endocrinology and Diabetes, Department of Medicine, College of Medicine, Aljouf University, Sakaka 72388, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hayder M.","family":"Al-kuraishy","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, College of Medicine, Al-Mustansiriyah University, Baghdad P.O. Box 14132, Iraq"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8284-8897","authenticated-orcid":false,"given":"Ali I.","family":"Al-Gareeb","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, College of Medicine, Al-Mustansiriyah University, Baghdad P.O. Box 14132, Iraq"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sadiq M.","family":"Al-Hamash","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, College of Medicine, Al-Mustansiriyah University, Baghdad P.O. Box 14132, Iraq"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2782-9615","authenticated-orcid":false,"given":"Michel","family":"De Waard","sequence":"additional","affiliation":[{"name":"Smartox Biotechnology, 6 Rue des Platanes, 38120 Saint-Egr\u00e8ve, France"},{"name":"L\u2019institut du Thorax, INSERM, CNRS, Universit\u00e9 de Nantes, 44007 Nantes, France"},{"name":"LabEx \u00abIon Channels, Science & Therapeutics\u00bb, Universit\u00e9 de Nice Sophia-Antipolis, 06560 Valbonne, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9040-5647","authenticated-orcid":false,"given":"Jean-Marc","family":"Sabatier","sequence":"additional","affiliation":[{"name":"Institut de Neurophysiopathologie (INP), Facult\u00e9 des Sciences M\u00e9dicales et Param\u00e9dicales, Aix-Marseille Universit\u00e9, CNRS UMR 7051, 27 Bd Jean Moulin, 13005 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9555-7300","authenticated-orcid":false,"given":"Hebatallah M.","family":"Saad","sequence":"additional","affiliation":[{"name":"Department of Pathology, Faculty of Veterinary Medicine, Matrouh University, Marsa Matruh 51744, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7817-425X","authenticated-orcid":false,"given":"Gaber","family":"El-Saber Batiha","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Therapeutics, Faculty of Veterinary Medicine, Damanhour University, Damanhour 22511, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Al-Kuraishy, H.M., Al-Gareeb, A.I., and Al-Buhadilly, A.K. (2018). Rosuvastatin improves vaspin serum levels in obese patients with acute coronary syndrome. Diseases, 6.","DOI":"10.3390\/diseases6010009"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"4","DOI":"10.4103\/IJCIIS.IJCIIS_49_20","article-title":"Statin therapy improves serum Annexin A1 levels in patients with acute coronary syndrome: A case-controlled study","volume":"11","author":"Samy","year":"2021","journal-title":"Int. J. Crit. Illn. Inj. Sci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"72","DOI":"10.4103\/2230-8210.172240","article-title":"Assessment of serum prolactin levels in acute myocardial infarction: The role of pharmacotherapy","volume":"20","author":"Awad","year":"2016","journal-title":"Indian J. Endocrinol. Metab."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"832","DOI":"10.1007\/s11096-022-01408-5","article-title":"Trimetazidine and COVID-19-induced acute cardiac injury: A missed key","volume":"44","author":"Welson","year":"2022","journal-title":"Int. J. Clin. Pharm."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"394","DOI":"10.36295\/ASRO.2021.24444","article-title":"Differential effects of statins on annexin A1 serum level in patients with acute coronary syndrome: A pleiotropic update","volume":"24","author":"Sami","year":"2021","journal-title":"Ann. Trop. Med. Public Health"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e000035","DOI":"10.1161\/HCV.0000000000000035","article-title":"An update on radial artery access and best practices for transradial coronary angiography and intervention in acute coronary syndrome: A scientific statement from the American Heart Association","volume":"11","author":"Mason","year":"2018","journal-title":"Circ. Cardiovasc. Interv."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2097","DOI":"10.1056\/NEJMoa1801174","article-title":"Alirocumab and cardiovascular outcomes after acute coronary syndrome","volume":"379","author":"Schwartz","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1007\/s00228-017-2242-2","article-title":"The leukotriene receptor antagonist montelukast and its possible role in the cardiovascular field","volume":"73","author":"Hoxha","year":"2017","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"ref_9","first-page":"121","article-title":"The liberation of a slow-reacting smooth muscle-stimulating substance in anaphylaxis","volume":"30","author":"Kellaway","year":"1940","journal-title":"Q. J. Exp. Physiol. Cogn. Med. Sci. Transl. Integr."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"174196","DOI":"10.1016\/j.ejphar.2021.174196","article-title":"Role of leukotriene pathway and montelukast in pulmonary and extrapulmonary manifestations of Covid-19: The enigmatic entity","volume":"904","author":"Almulaiky","year":"2021","journal-title":"Eur. J. Pharmacol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"eaat9453","DOI":"10.1126\/sciimmunol.aat9453","article-title":"The cysteinyl leukotriene 3 receptor regulates expansion of IL-25\u2013producing airway brush cells leading to type 2 inflammation","volume":"3","author":"Bankova","year":"2018","journal-title":"Sci. Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"104857","DOI":"10.1016\/j.phrs.2020.104857","article-title":"The role of the LTB4-BLT1 axis in health and disease","volume":"158","author":"He","year":"2020","journal-title":"Pharmacol. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"113225","DOI":"10.1016\/j.biopha.2022.113225","article-title":"Pentoxifylline and berberine mitigate diclofenac-induced acute nephrotoxicity in male rats via modulation of inflammation and oxidative stress","volume":"152","author":"Alorabi","year":"2022","journal-title":"Biomed. Pharmacother."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1488","DOI":"10.1164\/rccm.201906-1215OC","article-title":"Omalizumab for aspirin hypersensitivity and leukotriene overproduction in aspirin-exacerbated respiratory disease. A randomized controlled trial","volume":"201","author":"Hayashi","year":"2020","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1007\/s10787-022-00987-z","article-title":"COVID-19 and corticosteroids: A narrative review","volume":"30","author":"Batiha","year":"2022","journal-title":"Inflammopharmacology"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1038\/modpathol.2016.201","article-title":"Activating cysteinyl leukotriene receptor 2 (CYSLTR2) mutations in blue nevi","volume":"30","author":"Murali","year":"2017","journal-title":"Mod. Pathol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1016\/j.jaci.2009.06.035","article-title":"Genetics and pharmacogenetics of the leukotriene pathway","volume":"124","author":"Tantisira","year":"2009","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1097\/01.fpc.0000166456.84905.a0","article-title":"Association analysis of cysteinyl-leukotriene receptor 2 (CYSLTR2) polymorphisms with aspirin intolerance in asthmatics","volume":"15","author":"Park","year":"2005","journal-title":"Pharmacogenet. Genom."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1007\/s10787-022-00993-1","article-title":"A raising dawn of pentoxifylline in management of inflammatory disorders in Covid-19","volume":"30","author":"Jeandet","year":"2022","journal-title":"Inflammopharmacology"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"6093","DOI":"10.1021\/acs.jmedchem.5b00741","article-title":"Discovery of gemilukast (ONO-6950), a dual CysLT1 and CysLT2 antagonist as a therapeutic agent for asthma","volume":"58","author":"Itadani","year":"2015","journal-title":"J. Med. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1080\/10799893.2020.1835959","article-title":"Changes in expression of orphan receptors GPR99 and GPR107 during the development and establishment of hypertension in spontaneously hypertensive rats","volume":"41","author":"Huang","year":"2021","journal-title":"J. Recept. Signal Transduct."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1957","DOI":"10.1002\/glia.23807","article-title":"Regulation and signaling of the GPR17 receptor in oligodendroglial cells","volume":"68","author":"Lecca","year":"2020","journal-title":"Glia"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e022125","DOI":"10.1161\/JAHA.121.022125","article-title":"Cangrelor: Clinical data, contemporary use, and future perspectives","volume":"10","author":"Steg","year":"2021","journal-title":"J. Am. Heart Assoc."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Mansour, A., Bachelot-Loza, C., Nesseler, N., Gaussem, P., and Gouin-Thibault, I. (2020). P2Y12 inhibition beyond thrombosis: Effects on inflammation. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21041391"},{"key":"ref_25","first-page":"2387","article-title":"Montelukast inhibits RANKL-induced osteoclast formation and bone loss via CysLTR1 and P2Y12","volume":"18","author":"Kang","year":"2018","journal-title":"Mol. Med. Rep."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"263","DOI":"10.3389\/fphar.2019.00263","article-title":"Zafirlukast is a dual modulator of human soluble epoxide hydrolase and peroxisome proliferator-activated receptor \u03b3","volume":"10","author":"Diehl","year":"2019","journal-title":"Front. Pharmacol."},{"key":"ref_27","unstructured":"(2022, August 18). Fuse809 (talk)\u2014Own work, Public Domain. Available online: https:\/\/commons.wikimedia.org\/w\/index.php?curid=31613539."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/j.jaip.2020.07.052","article-title":"Risk of psychiatric adverse events among montelukast users","volume":"9","author":"Haug","year":"2021","journal-title":"J. Allergy Clin. Immunol. Pract."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/j.jpeds.2019.02.009","article-title":"Montelukast and neuropsychiatric events in children with asthma: A nested case\u2013control study","volume":"209","author":"Finkelstein","year":"2019","journal-title":"J. Pediatr."},{"key":"ref_30","unstructured":"Fox, C.W., Khaw, C.L., Gerke, A.K., and Lund, B.C. (2021). Montelukast and neuropsychiatric events\u2013a sequence symmetry analysis. J. Asthma, 1\u20137."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1002\/cpt.891","article-title":"Comprehensive pharmacogenomic study reveals an important role of UGT1A3 in montelukast pharmacokinetics","volume":"104","author":"Hirvensalo","year":"2018","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2432958","DOI":"10.1155\/2017\/2432958","article-title":"Role of the cysteinyl leukotrienes in the pathogenesis and progression of cardiovascular diseases","volume":"2017","author":"Colazzo","year":"2017","journal-title":"Mediat. Inflamm."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"S112","DOI":"10.1164\/ajrccm.161.supplement_1.ltta-22","article-title":"Leukotrienes in cardiovascular diseases","volume":"161","author":"Folco","year":"2000","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/j.ejphar.2013.12.024","article-title":"Montelukast and irbesartan ameliorate metabolic and hepatic disorders in fructose-induced metabolic syndrome in rats","volume":"724","author":"Ibrahim","year":"2014","journal-title":"Eur. J. Pharmacol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1038\/nrd2875","article-title":"Soluble epoxide hydrolase as a therapeutic target for cardiovascular diseases","volume":"8","author":"Imig","year":"2009","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1106","DOI":"10.1124\/pr.113.007781","article-title":"The pharmacology of the cytochrome P450 epoxygenase\/soluble epoxide hydrolase axis in the vasculature and cardiovascular disease","volume":"66","author":"Fleming","year":"2014","journal-title":"Pharmacol. Rev."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.phrs.2006.02.007","article-title":"Montelukast protects against renal ischemia\/reperfusion injury in rats","volume":"54","author":"Gedik","year":"2006","journal-title":"Pharmacol. Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.atherosclerosis.2008.11.012","article-title":"Anti-atherogenic effects of montelukast associated with reduced MCP-1 expression in a rabbit carotid balloon injury model","volume":"205","author":"Ge","year":"2009","journal-title":"Atherosclerosis"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1007\/s10557-009-6211-6","article-title":"Montelukast inhibits matrix metalloproteinases expression in atherosclerotic rabbits","volume":"23","author":"Liu","year":"2009","journal-title":"Cardiovasc. Drugs Ther."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1007\/s11883-010-0108-5","article-title":"Soluble epoxide hydrolase in atherosclerosis","volume":"12","author":"Wang","year":"2010","journal-title":"Curr. Atheroscler. Rep."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1665","DOI":"10.1161\/01.ATV.0000172632.96987.2d","article-title":"Association between 5-lipoxygenase expression and plaque instability in humans","volume":"25","author":"Cipollone","year":"2005","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1378\/chest.07-0831","article-title":"The effect of montelukast and low-dose theophylline on cardiovascular disease risk factors in asthmatics","volume":"132","author":"Allayee","year":"2007","journal-title":"Chest"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1007\/s10557-008-6140-9","article-title":"Leukotriene signaling in atherosclerosis and ischemia","volume":"23","year":"2009","journal-title":"Cardiovasc. Drugs Ther."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1038\/ng1311","article-title":"The gene encoding 5-lipoxygenase activating protein confers risk of myocardial infarction and stroke","volume":"36","author":"Helgadottir","year":"2004","journal-title":"Nat. Genet."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1161\/01.RES.0000028008.99774.7F","article-title":"Identification of 5-lipoxygenase as a major gene contributing to atherosclerosis susceptibility in mice","volume":"91","author":"Mehrabian","year":"2002","journal-title":"Circ. Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1159\/000296017","article-title":"Atorvastatin reduces plaque vulnerability in an atherosclerotic rabbit model by altering the 5-lipoxygenase pathway","volume":"115","author":"Zhou","year":"2010","journal-title":"Cardiology"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1161\/STROKEAHA.108.525733","article-title":"Genetic variation in the leukotriene pathway and carotid intima-media thickness: A 2-stage replication study","volume":"40","author":"Bevan","year":"2009","journal-title":"Stroke"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1056\/NEJMoa025079","article-title":"Arachidonate 5-lipoxygenase promoter genotype, dietary arachidonic acid, and atherosclerosis","volume":"350","author":"Dwyer","year":"2004","journal-title":"N. Engl. J. Med."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Nobili, E., Salvado, M.D., Folkersen, L., Castiglioni, L., Kastrup, J., Wetterholm, A., Tremoli, E., Hansson, G.K., Sironi, L., and Haeggstr\u00f6m, J.Z. (2012). Cysteinyl leukotriene signaling aggravates myocardial hypoxia in experimental atherosclerotic heart disease. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0041786"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"3274","DOI":"10.1038\/srep03274","article-title":"Cysteinyl leukotrienes regulate endothelial cell inflammatory and proliferative signals through CysLT2 and CysLT1 receptors","volume":"3","author":"Duah","year":"2013","journal-title":"Sci. Rep."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"30880","DOI":"10.1074\/jbc.R114.609248","article-title":"Multidrug resistance protein 1 (MRP1, ABCC1), a \u201cmultitasking\u201d ATP-binding cassette (ABC) transporter","volume":"289","author":"Cole","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2264","DOI":"10.4049\/jimmunol.156.6.2264","article-title":"Lipoxin A4 and B4 inhibit leukotriene-stimulated interactions of human neutrophils and endothelial cells","volume":"156","author":"Papayianni","year":"1996","journal-title":"J. Immunol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"6326","DOI":"10.1073\/pnas.0601223103","article-title":"Cysteinyl leukotriene 2 receptor and protease-activated receptor 1 activate strongly correlated early genes in human endothelial cells","volume":"103","author":"Uzonyi","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_54","unstructured":"Omede, A. (2015). Role of Alpha-Ketoglutarate Receptor G-Protein Coupled Receptor 99 (GPR99) in Cardiac Hypertrophy, The University of Manchester."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"92e","DOI":"10.1097\/PRS.0000000000009228","article-title":"Montelukast, an Antagonist of Cysteinyl Leukotriene Signaling, Impairs Burn Wound Healing","volume":"150","author":"Nguyen","year":"2022","journal-title":"Plast. Reconstr. Surg."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1186\/1472-6882-14-67","article-title":"DanQi Pill protects against heart failure through the arachidonic acid metabolism pathway by attenuating different cyclooxygenases and leukotrienes B4","volume":"14","author":"Wang","year":"2014","journal-title":"BMC Complement. Altern. Med."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/1476-511X-12-3","article-title":"Effects of soluble epoxide hydrolase inhibitor on the expression of fatty acid synthase in peripheral blood mononuclear cell in patients with acute coronary syndrome","volume":"12","author":"Zhao","year":"2013","journal-title":"Lipids Heal. Dis."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.prostaglandins.2018.07.005","article-title":"Association between the EPHX2 p. Lys55Arg polymorphism and prognosis following an acute coronary syndrome","volume":"138","author":"Cresci","year":"2018","journal-title":"Prostaglandins Other Lipid Mediat."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"H2128","DOI":"10.1152\/ajpheart.00428.2008","article-title":"Soluble epoxide hydrolase inhibition and gene deletion are protective against myocardial ischemia-reperfusion injury in vivo","volume":"295","author":"Motoki","year":"2008","journal-title":"Am. J. Physiol.-Heart Circ. Physiol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1161\/01.CIR.104.3.365","article-title":"Current concepts of the pathogenesis of the acute coronary syndromes","volume":"104","author":"Libby","year":"2001","journal-title":"Circulation"},{"key":"ref_61","first-page":"210","article-title":"Assessment of circulating PPAR-\u03b3 Level as a risk and diagnostic biomarker in Acute Coronary Syndrome","volume":"26","author":"Ali","year":"2018","journal-title":"J. Univ. Babylon Pure Appl. Sci."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"166","DOI":"10.4274\/jarem.galenos.2020.2931","article-title":"Effects of Leptin, Resistin, and PPAR-Gama Gene Variants on Obese Patients with Acute Coronary Syndrome in the Turkish Population","volume":"10","author":"Arat","year":"2020","journal-title":"JAREM. J. Acad. Res. Med."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"119203","DOI":"10.1016\/j.bbamcr.2021.119203","article-title":"Leukotriene C4 synthase is a novel PPAR\u03b3 target gene, and leukotriene C4 and D4 activate adipogenesis through cysteinyl LT1 receptors in adipocytes","volume":"1869","author":"Fujimori","year":"2022","journal-title":"Biochim. Biophys. Acta (BBA)-Mol. Cell Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1161\/01.ATV.0000252680.72734.10","article-title":"Association between a leukotriene C4 synthase gene promoter polymorphism and coronary artery calcium in young women: The Muscatine Study","volume":"27","author":"Iovannisci","year":"2007","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_65","first-page":"763","article-title":"Leukotriene biosynthesis by canine and human coronary arteries","volume":"241","author":"Piomelli","year":"1987","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1007\/BF02912454","article-title":"Metabolic and hemodynamic effects of peptide leukotriene C4 and D4 in man","volume":"27","author":"Vigorito","year":"1997","journal-title":"Int. J. Clin. Lab. Res."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1007\/s00109-012-0904-1","article-title":"Cysteinyl leukotriene signaling through perinuclear CysLT1 receptors on vascular smooth muscle cells transduces nuclear calcium signaling and alterations of gene expression","volume":"90","author":"Eaton","year":"2012","journal-title":"J. Mol. Med."},{"key":"ref_68","first-page":"e32","article-title":"Differential Leukotriene Receptor Expression and Calcium Responses in Endothelial Cells and Macrophages Indicate 5-Lipoxygenase\u2013Dependent Circuits of Inflammation and Atherogenesis","volume":"23","author":"Spanbroek","year":"2003","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1841","DOI":"10.1056\/NEJMra071371","article-title":"Leukotrienes","volume":"357","author":"Henderson","year":"2007","journal-title":"N. Engl. J. Med."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1097\/00019501-199310000-00009","article-title":"Enhanced excretion of urinary leukotriene E4 in coronary artery disease and after coronary artery bypass surgery","volume":"4","author":"Allen","year":"1993","journal-title":"Coron. Artery Dis."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1161\/ATVBAHA.113.302536","article-title":"Multiple-site activation of the cysteinyl leukotriene receptor 2 is required for exacerbation of ischemia\/reperfusion injury","volume":"34","author":"Ni","year":"2014","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.cardiores.2005.06.007","article-title":"Cytochrome P450 and arachidonic acid metabolites: Role in myocardial ischemia\/reperfusion injury revisited","volume":"68","author":"Gross","year":"2005","journal-title":"Cardiovasc. Res."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1084\/jem.155.2.535","article-title":"Resting macrophages produce distinct metabolites from exogenous arachidonic acid","volume":"155","author":"Scott","year":"1982","journal-title":"J. Exp. Med."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1016\/j.yjmcc.2010.11.013","article-title":"Inhibition of leukotriene C4 action reduces oxidative stress and apoptosis in cardiomyocytes and impedes remodeling after myocardial injury","volume":"50","author":"Becher","year":"2011","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"H2068","DOI":"10.1152\/ajpheart.1994.266.5.H2068","article-title":"Effects of LTD4 and its specific antagonist L-660,711 in isolated rat hearts with chronic myocardial infarction","volume":"266","author":"Han","year":"1994","journal-title":"Am. J. Physiol.-Heart Circ. Physiol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1124\/jpet.111.186031","article-title":"A selective cysteinyl leukotriene receptor 2 antagonist blocks myocardial ischemia\/reperfusion injury and vascular permeability in mice","volume":"339","author":"Ni","year":"2011","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"592","DOI":"10.2353\/ajpath.2008.070834","article-title":"Endothelial cysteinyl leukotriene 2 receptor expression mediates myocardial ischemia-reperfusion injury","volume":"172","author":"Jiang","year":"2008","journal-title":"Am. J. Pathol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1124\/jpet.113.207647","article-title":"Is GPR17 a P2Y\/leukotriene receptor? examination of uracil nucleotides, nucleotide sugars, and cysteinyl leukotrienes as agonists of GPR17","volume":"347","author":"Qi","year":"2013","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1161\/01.CIR.85.1.230","article-title":"Increased urinary leukotriene excretion in patients with cardiac ischemia. In vivo evidence for 5-lipoxygenase activation","volume":"85","author":"Carry","year":"1992","journal-title":"Circulation"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"100629","DOI":"10.1016\/j.conctc.2020.100629","article-title":"Design and rationale of FLAVOUR: A phase IIa efficacy study of the 5-lipoxygenase activating protein antagonist AZD5718 in patients with recent myocardial infarction","volume":"19","author":"Prescott","year":"2020","journal-title":"Contemp. Clin. Trials Commun."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1093\/cvr\/27.5.770","article-title":"Leukotrienes D4 and E4 produced in myocardium impair coronary flow and ventricular function after two hours of global ischaemia in rat heart","volume":"27","author":"Lee","year":"1993","journal-title":"Cardiovasc. Res."},{"key":"ref_82","first-page":"335","article-title":"Myocardial protection by the leukotriene synthesis inhibitor BAY X1005: Importance of transcellular biosynthesis of cysteinyl-leukotrienes","volume":"276","author":"Rossoni","year":"1996","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_83","first-page":"223","article-title":"Role of eicosanoid inhibition of ischemia reperfusion injury: Intact and isolated rat heart studies","volume":"19","author":"Shekher","year":"1997","journal-title":"Methods Find. Exp. Clin. Pharmacol."},{"key":"ref_84","first-page":"58","article-title":"Antagonism of leukotriene B4 receptors does not limit canine myocardial infarct size","volume":"253","author":"Hahn","year":"1990","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1038\/ng1692","article-title":"A variant of the gene encoding leukotriene A4 hydrolase confers ethnicity-specific risk of myocardial infarction","volume":"38","author":"Helgadottir","year":"2006","journal-title":"Nat. Genet."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"8749","DOI":"10.1096\/fj.202000041R","article-title":"Leukotriene B4 receptor 1 exacerbates inflammation following myocardial infarction","volume":"34","author":"Horii","year":"2020","journal-title":"FASEB J."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"956","DOI":"10.1016\/j.biopha.2018.07.033","article-title":"Potential role of leukotriene receptor antagonists in reducing cardiovascular and cerbrovascular risk: A systematic review of human clinical trials and in vivo animal studies","volume":"106","author":"Hoxha","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1177\/0960327115591372","article-title":"Montelukast attenuates lipopolysaccharide-induced cardiac injury in rats","volume":"35","author":"Khodir","year":"2016","journal-title":"Hum. Exp. Toxicol."},{"key":"ref_89","first-page":"43","article-title":"Leukotriene biosynthesis in coronary artery disease: Results of the Leukotrienes and Thromboxane In Myocardial Infarction (LTIMI) study","volume":"128","author":"Rzeszutko","year":"2018","journal-title":"Pol. Arch. Med. Wewn\u0119trznej Pol. Arch. Intern. Med."},{"key":"ref_90","unstructured":"Vroegindewey, M.M., Buljubasic, N., Oemrawsingh, R.M., Kardys, I., Asselbergs, F.W., van der Harst, P., Umans, V.A., Kietselaer, B., Lenderink, T., and Liem, A. (2019). MAPK-cascade stimulating biomarkers in relation to recurrent coronary events following an acute coronary syndrome. The Prognostic Value of Coronary Imaging and Biomarkers in Ischemic Heart Disease, Gildeprint."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1111\/j.1365-2567.2008.02827.x","article-title":"Toll-like receptor-4 and mitogen-activated protein kinase signal system are involved in activation of dendritic cells in patients with acute coronary syndrome","volume":"125","author":"Wang","year":"2008","journal-title":"Immunology"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1007\/s00395-011-0172-1","article-title":"Mitogen-activated protein kinases activation in T lymphocytes of patients with acute coronary syndromes","volume":"106","author":"Indolfi","year":"2011","journal-title":"Basic Res. Cardiol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.yjmcc.2020.09.009","article-title":"Glycogen synthase kinase-3\u03b2 inhibition alleviates activation of the NLRP3 inflammasome in myocardial infarction","volume":"149","author":"Wang","year":"2020","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1097\/FJC.0000000000000717","article-title":"NLRP3 inflammasome in acute myocardial infarction","volume":"74","author":"Mauro","year":"2019","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.biocel.2017.01.001","article-title":"Vascular endothelial cells senescence is associated with NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome activation via reactive oxygen species (ROS)\/thioredoxin-interacting protein (TXNIP) pathway","volume":"84","author":"Yin","year":"2017","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1007\/s11892-017-0865-4","article-title":"The mTOR signaling pathway in myocardial dysfunction in type 2 diabetes mellitus","volume":"17","author":"Suhara","year":"2017","journal-title":"Curr. Diab. Rep."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1007\/s00395-017-0646-x","article-title":"Methylglyoxal-derived advanced glycation end products contribute to negative cardiac remodeling and dysfunction post-myocardial infarction","volume":"112","author":"Blackburn","year":"2017","journal-title":"Basic Res. Cardiol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.taap.2018.09.012","article-title":"Montelukast attenuates rotenone-induced microglial activation\/p38 MAPK expression in rats: Possible role of its antioxidant, anti-inflammatory and antiapoptotic effects","volume":"358","author":"Mansour","year":"2018","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1090","DOI":"10.1213\/ANE.0000000000000174","article-title":"Montelukast attenuates neuropathic pain through inhibiting p38 mitogen-activated protein kinase and nuclear factor-kappa B in a rat model of chronic constriction injury","volume":"118","author":"Zhou","year":"2014","journal-title":"Anesth. Analg."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"7894","DOI":"10.1080\/21655979.2022.2051689","article-title":"Montelukast ameliorated pemetrexed-induced cytotoxicity in hepatocytes by mitigating endoplasmic reticulum (ER) stress and nucleotide oligomerization domain-like receptor protein 3 (NLRP3) activation","volume":"13","author":"Fei","year":"2022","journal-title":"Bioengineered"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"120707","DOI":"10.1016\/j.lfs.2022.120707","article-title":"Ameliorative effect of montelukast against carbon tetrachloride-induced hepatotoxicity: Targeting NLRP3 inflammasome pathway","volume":"304","author":"Zaghloul","year":"2022","journal-title":"Life Sci."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1080\/15384047.2018.1529112","article-title":"Montelukast enhances cytocidal effects of carfilzomib in multiple myeloma by inhibiting mTOR pathway","volume":"20","author":"Tong","year":"2019","journal-title":"Cancer Biol. Ther."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.intimp.2018.12.056","article-title":"Zafirlukast attenuates advanced glycation end-products (AGEs)-induced degradation of articular extracellular matrix (ECM)","volume":"68","author":"Lei","year":"2019","journal-title":"Int. Immunopharmacol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/j.thromres.2011.12.026","article-title":"Thrombosis and acute coronary syndrome","volume":"129","author":"Abbate","year":"2012","journal-title":"Thromb. Res."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"113","DOI":"10.3132\/dvdr.2005.018","article-title":"Inflammation, thrombosis and acute coronary syndromes","volume":"2","author":"Carter","year":"2005","journal-title":"Diabetes Vasc. Dis. Res."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1076029618824418","DOI":"10.1177\/1076029618824418","article-title":"Relationship between C-reactive protein to albumin ratio and thrombus burden in patients with acute coronary syndrome","volume":"25","author":"Duman","year":"2019","journal-title":"Clin. Appl. Thromb. Hemost."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1093\/ehjcvp\/pvaa009","article-title":"Antithrombotic therapy in patients with acute coronary syndrome complicated by cardiogenic shock or out-of-hospital cardiac arrest: A joint position paper from the European Society of Cardiology (ESC) Working Group on Thrombosis, in association with the Acute Cardiovascular Care Association (ACCA) and European Association of Percutaneous Cardiovascular Interventions (EAPCI)","volume":"7","author":"Gorog","year":"2021","journal-title":"Eur. Heart J. Cardiovasc. Pharmacother."},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Babalghith, A.O., Al-kuraishy, H.M., Al-Gareeb, A.I., De Waard, M., Sabatier, J.-M., Saad, H.M., and Batiha, G.E.-S. (2022). The Potential Role of Growth Differentiation Factor 15 in COVID-19: A Corollary Subjective Effect or Not?. Diagnostics, 12.","DOI":"10.3390\/diagnostics12092051"},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Wang, D., Zhou, Y., Qi, Y., Song, M., Yao, H., Liao, C., Lin, H., Huang, M., Zhuo, D., and Jiang, L. (2021). Antithrombotic Effects of Montelukast by Targeting Coagulation Factor XIa, Preprint.","DOI":"10.21203\/rs.3.rs-477725\/v1"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1376","DOI":"10.1096\/fj.08-116202","article-title":"Differential inflammatory activity across human abdominal aortic aneurysms reveals neutrophilderived leukotriene B4 as a major chemotactic factor released from the intraluminal thrombus","volume":"23","author":"Houard","year":"2009","journal-title":"FASEB J."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"3304","DOI":"10.1161\/01.CIR.92.11.3304","article-title":"Peptido-leukotrienes are potent agonists of von Willebrand factor secretion and P-selectin surface expression in human umbilical vein endothelial cells","volume":"92","author":"Datta","year":"1995","journal-title":"Circulation"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1007\/s13311-019-00787-4","article-title":"Early and sustained increases in leukotriene B4 levels are associated with poor clinical outcome in ischemic stroke patients","volume":"17","author":"Chan","year":"2020","journal-title":"Neurotherapeutics"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"H153","DOI":"10.1152\/ajpheart.1988.255.1.H153","article-title":"Synergistic effects of LTC4 and TxA2 on coronary flow and myocardial function","volume":"255","author":"Nichols","year":"1988","journal-title":"Am. J. Physiol.-Heart Circ. Physiol."},{"key":"ref_114","doi-asserted-by":"crossref","unstructured":"Al-kuraishy, H.M., Batiha, G.E.-S., Faidah, H., Al-Gareeb, A.I., Saad, H.M., and Simal-Gandara, J. (2022). Pirfenidone and post-Covid-19 pulmonary fibrosis: Invoked again for realistic goals. Inflammopharmacology, 1\u201310.","DOI":"10.1007\/s10787-022-01027-6"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"976","DOI":"10.1111\/jth.14734","article-title":"Activation of metabolite receptor GPR91 promotes platelet aggregation and transcellular biosynthesis of leukotriene C4","volume":"18","author":"Tang","year":"2020","journal-title":"J. Thromb. Haemost."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/15\/9\/1147\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:31:29Z","timestamp":1760142689000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/15\/9\/1147"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,14]]},"references-count":115,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2022,9]]}},"alternative-id":["ph15091147"],"URL":"https:\/\/doi.org\/10.3390\/ph15091147","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,14]]}}}