Montelukast, an available and safe anti-asthmatic drug, prevents maladaptive remodelling and maintains cardiac functionality following myocardial infarction
Abstract Preclinical and clinical data indicate that the 5-lipoxygenase pathway becomes activated in cardiovascular diseases suggesting an important role of CysLTs in atherosclerosis and in its ischemic complications. This study aims to investigate the effects of montelukast, a CysLTR-1 antagonist,...
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| Format: | Article |
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Nature Portfolio
2024-02-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-024-53936-x |
| _version_ | 1797274957421477888 |
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| author | Majeda Muluhie Laura Castiglioni Joanna Rzemieniec Benedetta Mercuriali Paolo Gelosa Luigi Sironi |
| author_facet | Majeda Muluhie Laura Castiglioni Joanna Rzemieniec Benedetta Mercuriali Paolo Gelosa Luigi Sironi |
| author_sort | Majeda Muluhie |
| collection | DOAJ |
| description | Abstract Preclinical and clinical data indicate that the 5-lipoxygenase pathway becomes activated in cardiovascular diseases suggesting an important role of CysLTs in atherosclerosis and in its ischemic complications. This study aims to investigate the effects of montelukast, a CysLTR-1 antagonist, in a mouse model of myocardial infarction (MI). C57BL/6N female mice were subjected to coronary artery ligation and received montelukast (10 mg/kg/day, intraperitoneal) or vehicle. Montelukast exerted beneficial effects in the infarcted area, decreasing mRNA expression of inflammatory genes, such Il1β and Ccl2 (p < 0.05), at 48 h after MI, and reducing infarct size and preventing ischemic wall thinning (p < 0.05) at 4 weeks. Furthermore, montelukast counteracted maladaptive remodelling of whole heart. Indeed, montelukast reduced LV mass (p < 0.05) and remote wall thickening (p < 0.05), and improved cardiac pumping function, as evidenced by increased global ejection fraction (p < 0.01), and regional contractility in infarcted (p < 0.05) and in remote non-infarcted (p < 0.05) myocardium. Finally, montelukast prevented cardiomyocytes hypertrophy (p < 0.05) in remote myocardium, reducing the phosphorylation of GSK3β, a regulator of hypertrophic pathway (p < 0.05). Our data strongly demonstrate the ability of montelukast to contrast the MI-induced maladaptive conditions, thus sustaining cardiac contractility. The results provide evidences for montelukast “repurposing” in cardiovascular diseases and in particular in myocardial infarction. |
| first_indexed | 2024-03-07T15:07:33Z |
| format | Article |
| id | doaj.art-c4f7702d880441b0937da2784b0e4be9 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-07T15:07:33Z |
| publishDate | 2024-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-c4f7702d880441b0937da2784b0e4be92024-03-05T18:52:02ZengNature PortfolioScientific Reports2045-23222024-02-0114111210.1038/s41598-024-53936-xMontelukast, an available and safe anti-asthmatic drug, prevents maladaptive remodelling and maintains cardiac functionality following myocardial infarctionMajeda Muluhie0Laura Castiglioni1Joanna Rzemieniec2Benedetta Mercuriali3Paolo Gelosa4Luigi Sironi5Department of Pharmaceutical Sciences, University of MilanDepartment of Pharmaceutical Sciences, University of MilanDepartment of Pharmaceutical Sciences, University of MilanDepartment of Pharmaceutical Sciences, University of MilanDepartment of Pharmaceutical Sciences, University of MilanDepartment of Pharmaceutical Sciences, University of MilanAbstract Preclinical and clinical data indicate that the 5-lipoxygenase pathway becomes activated in cardiovascular diseases suggesting an important role of CysLTs in atherosclerosis and in its ischemic complications. This study aims to investigate the effects of montelukast, a CysLTR-1 antagonist, in a mouse model of myocardial infarction (MI). C57BL/6N female mice were subjected to coronary artery ligation and received montelukast (10 mg/kg/day, intraperitoneal) or vehicle. Montelukast exerted beneficial effects in the infarcted area, decreasing mRNA expression of inflammatory genes, such Il1β and Ccl2 (p < 0.05), at 48 h after MI, and reducing infarct size and preventing ischemic wall thinning (p < 0.05) at 4 weeks. Furthermore, montelukast counteracted maladaptive remodelling of whole heart. Indeed, montelukast reduced LV mass (p < 0.05) and remote wall thickening (p < 0.05), and improved cardiac pumping function, as evidenced by increased global ejection fraction (p < 0.01), and regional contractility in infarcted (p < 0.05) and in remote non-infarcted (p < 0.05) myocardium. Finally, montelukast prevented cardiomyocytes hypertrophy (p < 0.05) in remote myocardium, reducing the phosphorylation of GSK3β, a regulator of hypertrophic pathway (p < 0.05). Our data strongly demonstrate the ability of montelukast to contrast the MI-induced maladaptive conditions, thus sustaining cardiac contractility. The results provide evidences for montelukast “repurposing” in cardiovascular diseases and in particular in myocardial infarction.https://doi.org/10.1038/s41598-024-53936-x |
| spellingShingle | Majeda Muluhie Laura Castiglioni Joanna Rzemieniec Benedetta Mercuriali Paolo Gelosa Luigi Sironi Montelukast, an available and safe anti-asthmatic drug, prevents maladaptive remodelling and maintains cardiac functionality following myocardial infarction Scientific Reports |
| title | Montelukast, an available and safe anti-asthmatic drug, prevents maladaptive remodelling and maintains cardiac functionality following myocardial infarction |
| title_full | Montelukast, an available and safe anti-asthmatic drug, prevents maladaptive remodelling and maintains cardiac functionality following myocardial infarction |
| title_fullStr | Montelukast, an available and safe anti-asthmatic drug, prevents maladaptive remodelling and maintains cardiac functionality following myocardial infarction |
| title_full_unstemmed | Montelukast, an available and safe anti-asthmatic drug, prevents maladaptive remodelling and maintains cardiac functionality following myocardial infarction |
| title_short | Montelukast, an available and safe anti-asthmatic drug, prevents maladaptive remodelling and maintains cardiac functionality following myocardial infarction |
| title_sort | montelukast an available and safe anti asthmatic drug prevents maladaptive remodelling and maintains cardiac functionality following myocardial infarction |
| url | https://doi.org/10.1038/s41598-024-53936-x |
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