Backgrounds: Aortic aneurysm and dissection (AAD) are caused by weaking vessel wall and depletion of vascular smooth muscle cells (VSMC). Osteopontin (OPN) causes the onset and exacerbation of AAD by increasing expression of matrix metalloproteinases (MMPs). Fluoroquinolones are the most common used antibiotics. On the other hand, clinical studies have indicated that fluoroquinolones may be associated with an increased risk of AAD. In this study, we examined the effects of moxifloxacin (MFLX), one of the fluoroquinolones, on the development of AAD in model mice.
Methods and results: C57BL/6J mice (4-week-old) were fed a high-fat diet. At 8 weeks of age, the mice were started to infuse with saline or angiotensin Ⅱ (1000 ng min^-1 day^-1) via osmotic minipumps for 4 weeks and then these mice were orally administered water (vehicle) or MFLX (30 and 100 mg min^-1 day^-1) for last 3 weeks. AAD lesions were histologically analyzed. MFLX (30 and 100 mg min^-1 day^-1) induced AAD formation and elastin degradation in aortic tissues by H&E staining and EVG staining. Additionally, by western blot analyses, MFLX (100 mg min^-1 day^-1) decreased the protein expression of SM22a, one of the VSMC markers, in aortic tissues compared to vehicle and MFLX (30 mg min^-1 day^-1). Furthermore, MFLX (30 and 100 mg min^-1 day^-1) increased the protein expression of OPN, MMP-2, and -9 in aortic tissues.
Conclusion: MFLX decreased the expression of SM22a and increased the expression of OPN and MMPs in aortic tissues from AAD model mice. Therefore, MFLX may induce the onset of AAD by weakening the aortic media.