montelukast and Aortic-Aneurysm

The pathogenesis of abdominal aortic aneurysm (AAA) is characterized by atherosclerosis with chronic inflammation in the aortic wall. Montelukast is a selective cys-LT 1 receptor antagonist that can suppress atherosclerotic diseases. We evaluated the in vitro properties of montelukast and its in vivo activities in an angiotensin II-infused apolipoprotein E-deficient (apoE. The mouse monocyte/macrophage cell line J774A.1 was used in vitro. M1 macrophages were treated with montelukast, and gene expressions of inflammatory cytokines were measured. Macrophages were cultured with montelukast, then gene expressions of arginase-1 and IL (interleukin)-10 were assessed by quantitative polymerase chain reaction, arginase-1 was measured by fluorescence-activated cell sorting, and IL-10 concentration was analyzed by enzyme-linked immunosorbent assay. In vivo, one group (Mont, n=7) received oral montelukast (10 mg/kg/day) for 28 days, and the other group (Saline, n=7) was given normal Saline as a control for the same period. Aortic diameters, activities of matrix metalloproteinases (MMPs), cytokine concentrations, and the number of M2 macrophages were analyzed.. Relative to control, montelukast significantly suppressed gene expressions of MMP-2, MMP-9, and IL-1. Montelukast induces M2 macrophage polarization and prevents AAA formation in apoE

Topics: Acetates; Animals; Aorta; Aortic Aneurysm; Arginase; Cell Line; Cell Polarity; Chemokines; Cyclopropanes; Gene Expression Regulation; Inflammation Mediators; Intercellular Signaling Peptides and Proteins; Interleukin-10; Macrophages; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Mice, Inbred C57BL; Quinolines; Receptors, Leukotriene; Sulfides; Tumor Necrosis Factor-alpha