Vascular endothelial dysfunction is involved in the fluoroquinolone-associated aortic aneurysm and dissection

Abstract

Aortic aneurysm and dissection (AAD) are common arterial diseases with high mortality. Recently, AAD have been reported as adverse events associated with fluoroquinolones. Previous studies showed fluoroquinolones could induce AAD through arterial media disorder, but the influence of fluoroquinolones to vascular endothelium is unknown. The aim of current study is to evaluate the effect of fluoroquinolone to vascular endothelium on the development of AAD. We analyzed the association in clinical situation between fluoroquinolones and AAD using VigiBase, the World Health Organization’s global database. We evaluated whether levofloxacin (LVFX) affects the AAD development using human umbilical vein endothelial cells (HUVECs) and aortic dissection model mice which induced by three drugs; nitric oxide synthase inhibitor, angiotensin II, and lysyl oxidase inhibitor. VigiBase analysis showed that the fluoroquinolones had the association of high reporting rate of AAD. Although LVFX did not significantly increase the incidence of AAD in mice, LVFX treatment increased VCAM-1 expression in HUVECs. Our results suggested that the endothelial dysfunction might be one candidate mechanism of fluoroquinolone-associated AAD.