Montelukast, an available and safe anti-asthmatic drug, prevents maladaptive remodelling and maintains cardiac functionality following myocardial infarction
Articolo
Data di Pubblicazione:
2024
Citazione:
Montelukast, an available and safe anti-asthmatic drug, prevents maladaptive remodelling and maintains cardiac functionality following myocardial infarction / M. Muluhie, L. Castiglioni, J. Rzemieniec, B. Mercuriali, P. Gelosa, L. Sironi. - In: SCIENTIFIC REPORTS. - ISSN 2045-2322. - 14:1(2024 Feb 09), pp. 3371.1-3371.12. [10.1038/s41598-024-53936-x]
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.
Tipologia IRIS:
01 - Articolo su periodico
Elenco autori:
M. Muluhie, L. Castiglioni, J. Rzemieniec, B. Mercuriali, P. Gelosa, L. Sironi
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