Moxifloxacin induces aortic aneurysm and dissection by increasing osteopontin in mice

Fluoroquinolones are one of the most frequently prescribed antibiotics. However, their use increases the risk of Aortic aneurysm and dissection (AAD). The mechanism underlying this effect remains unclear. AAD are caused by weakening of the aortic wall and loss of vascular smooth muscle cells. Osteopontin is involved in the occurrence and development of AAD. The aim of the present study was to examine the role of moxifloxacin, a fluoroquinolone, in the occurrence of AAD using a moderate-severity AAD mouse model. Four-week-old male C57BL/6J mice were fed a high-fat diet. At 8 weeks of age, the mice were infused with saline or angiotensin II (1000 ng kg^-1 min^-1) via osmotic minipumps for 4 weeks, and then orally administered water (vehicle) or moxifloxacin (30 and 100 mg kg^-1 day^-1) for another 3 weeks. Moxifloxacin (30 and 100 mg kg^-1 day^-1) induced AAD and elastin degradation in aortic tissues, as revealed by hematoxylin and eosin staining and elastica-van Gieson staining. Additionally, immunohistochemical staining and Western blot analyses showed that moxifloxacin 100 mg kg^-1 day^-1 decreased the protein expression of smooth muscle protein 22α, one of the markers of the contractile phenotype of vascular smooth muscle cells, in aortic tissues compared to vehicle and moxifloxacin 30 mg kg^-1 day^-1. Furthermore, moxifloxacin (100 mg kg^-1 day^-1) increased the protein expression of osteopontin and matrix metalloproteinases-2 in the aortic tissues when compared to control. Moxifloxacin may induce the onset of AAD and weakening of the aortic media by increasing the expression of osteopontin and matrix metalloproteinase-2 and decreasing that of smooth muscle protein 22α in aortic tissue.