Objective: The pathogenesis of aortic aneurysm (AA) is associated with chronic inflammation in the aortic wall with increased levels of matrix metalloproteinases (MMPs). Clarithromycin (CAM) has been reported to suppresses MMP activity. In this study, we investigated whether CAM could prevent the formation and rupture of AA. Methods: Male apolipoprotein E-deficient mice (28-30 weeks of age) were infused with angiotensin II for 28 days. CAM (100 mg/kg/d) or saline (as a control) was administered orally to the mice every day (CAM group, n = 13; control group, n = 13). After the administration period, the aortic diameter, elastin content, macrophage infiltration, MMP levels, and levels of inflammatory cytokines, including nuclear factor κB (NF-κB), were measured. Results: The aortic diameter was significantly suppressed in the CAM group (P <.001). No rupture death was observed in the CAM group in contrast to five deaths (38%) in the control group (P <.01). CAM significantly suppressed the degradation of aortic elastin (56.3% vs 16.5%; P <.001) and decreased the infiltration of inflammatory macrophages (0.05 vs 0.16; P <.01). Compared with the controls, the enzymatic activity of MMP-2 and MMP-9 was significantly reduced in the CAM group (MMP-2, 0.15 vs 0.56 [P <.01]; MMP-9, 0.12 vs 0.60 [P <.01]), and the levels of interleukin 1β (346.6 vs 1066.0; P <.05), interleukin 6 (128.4 vs 346.2; P <.05), and phosphorylation of NF-κB were also decreased (0.3 vs 2.0; P <.01). Conclusions: CAM suppressed the progression and rupture of AA through the suppression of inflammatory macrophage infiltration, a reduction in MMP-2 and MMP-9 activity, and the inhibition of elastin degradation associated with the suppression of NF-κB phosphorylation. Clinical Relevance: This article shows that high-dose clarithromycin (CAM) suppressed aortic aneurysm formation and rupture. Fortunately, no mice had adverse effects of CAM in the laboratory test. For clinical relevance, we will try a low dose of CAM for the same model of mice, such as 10 mg/kg/d or less. Although we think we need to try bigger animals, such as a pig, we have no study design of an aortic aneurysm model for big animals.
All Science Journal Classification (ASJC) codes
- Cardiology and Cardiovascular Medicine