Combination Therapy With Clarithromycin and Montelukast Suppresses the Progression of Aortic Aneurysms in Mice With Chronic Obstructive Pulmonary Disease.

Background: Chronic obstructive pulmonary disease (COPD) is a known risk factor for aortic aneurysm (AA) enlargement and rupture. This study investigated the effects of clarithromycin (CAM) and montelukast (Mont), which are medications used to treat COPD, on AA progression in a murine model of COPD.

Methods and results: Apolipoprotein E-deficient mice, aged 28-40 weeks, were infused with angiotensin II by osmotic pumps to induce AA formation. Some of them received COPD induction through a single dose of porcine pancreatic elastase via the trachea. Mice were divided into 3 groups: AA (n=16; AA only, treated with saline); AA-C (n=10; AA and COPD, treated with saline); and AA-Cm (n=10; AA and COPD, treated with CAM and Mont). CAM and Mont were administered orally on a daily basis. After 28 days, aortic diameter, elastin content, matrix metalloproteinase (MMP) activity, and inflammatory markers were evaluated. The AA-C group exhibited significantly larger aneurysm diameter than the AA group (2.41 vs. 1.97 mm; P<0.05). Compared with the AA-C group, the AA-Cm group had higher elastin content (46.8 vs. 32.3%; P<0.01), decreased TNF-α level (115.5 vs. 141.0 pg/mL; P<0.05), reduced MMP-9 activity (54.8 vs. 75.4 pg/mL; P<0.01), and lower M1/M2 macrophage ratio.

Conclusions: CAM and Mont attenuate AA progression in COPD by reducing inflammation, preserving elastin, and increasing infiltrated M2 macrophages, suggesting they have a therapeutic potential.