Abstract 12947: Clarithromycin Prevents Progression & Rupture of Aortic Aneurysm
Introduction: The pathogenesis of aortic aneurysm (AA) is mainly characterized by chronic inflammation in the aortic wall with accumulation of macrophages and degradation of extracellular matrix (ECM) with increased matrix metalloproteinases (MMP), particularly MMP-2 & -9, resulting in the degradation of collagen, elastin fragmentation and smooth muscle cell apoptosis. Meanwhile, clarithromycin (CAM) is well-known potent antibiotic, otherwise, CAM has been reported to have multiple biologic effects, such as alteration of inflammatory factors including MMP-2 & -9. In this study, we investigated the effects of clarithromycin on induced AA in mice.
Methods: Male aged apolipoprotein E deficient (ApoE-/-) mice were infused 1000 ng/kg/min Angiotensin II for 28 days to induce AA. In the CAM-treated group (CAM group: n=13), the mice were dosed with CAM (100 mg/kg/day) by the gastric tube every day. In the control group (CONT; n=13), saline was administrated. Echo-aortography was performed every week to measure aortic diameters. The aneurysm induced aorta was removed and evaluated. Elastica van-Gieson stain was performed for evaluation of ECM in the aortic wall. The elastin content of the aorta were measured. Infiltrations of inflammatory macrophages were evaluated by immunofluorescence staining against CD 206 & F4/80. Gelatin zymography was performed to evaluate MMP-2 & -9 activities in aortic tissues.
Results: Echo-aortography showed the aortic diameters were significantly attenuated in CAM group. The incidence of AA in CONT was 100%, which was significantly decreased to 23% in CAM group. No ruptured death was observed in CAM group in contrast to 5 ruptured deaths in CONT (Log Rank test, p=0.01). CAM significantly suppressed degradation of aortic elastin (56.3% & 16.5%, p<0.001) & decreased infiltration of inflammatory macrophages (5.3% & 16.0%, p=0.005). CAM significantly attenuated MMP-2 (0.15 & 0.56, p<0.001) & MMP-9 activities (0.12 & 0.60, p<0.001) respectively.
Conclusions: CAM prevented the development of AA & rupture through suppression of inflammatory macrophages infiltration, decreased MMP-2 & -9, & preserved elastin content.
Author Disclosures: W. Uchida: None. A. Yamawaki-Ogata: None. H. Oshima: None. A. Usui: None. Y. Narita: None.
- © 2016 by American Heart Association, Inc.