Back to 2026 Abstracts
Ciprofloxacin Exposure Promotes Aortic Dissection and Arterial Rupture in a Mouse Model of Vascular Ehlers-Danlos Syndrome
Scott A. LeMaire2, *Lin Zhang
1, *Chen Zhang
1, *Deborah Vela
1, Joseph S. Coselli
1, *Ying Shen
11Surgery, Baylor College of Medicine, Houston, Texas; 2Cardiothoracic Surgery, Geisinger, Danville, Pennsylvania
Objective: While data support that fluoroquinolones exacerbate lethal sequela in the setting of some types of aortic pathology, the potential danger of these drugs has not been studied in the context of vascular Ehlers-Danlos syndrome (vEDS). Given the impracticality of rigorous clinical studies evaluating this concern, experiments to determine whether there is a plausible biological explanation provide essential translational evidence that can guide clinical decision making. Consequently, we tested the hypothesis that ciprofloxacin exposure increases the incidence of arterial dissection and rupture in vEDS mice.
Methods: vEDS mice carry a mutation in the gene encoding type III collagen components (
Col3a1[G209S/WT]) that is analogous to a mutation identified in vEDS patients. Eight-week-old male and female vEDS mice were randomly assigned to receive either ciprofloxacin (n=25) or vehicle control (n=24) through daily gavage for 2 weeks. The dose of ciprofloxacin (100 mg/kg/day) was equivalent to that used for common indications in humans, adjusted for mice based on allometric scaling. Male and female wild-type littermates (
Col3a1[WT/WT]) received either vehicle or ciprofloxacin and served as additional controls. Mice were sacrificed after being monitored for 4 weeks. We compared groups based on survival, incidence of dissection and rupture of the aorta and branch arteries, and levels of collagen (picrosirius red), lysyl oxidase (LOX), and macrophages (CD68) in ascending aortic tissue sections.
Results: All vEDS mice that received vehicle and all littermate controls survived the 4-week study period. In contrast, vEDS mice that received ciprofloxacin had a high rate of death (44% [11/25] vs 0% [0/24] in vehicle-treated vEDS mice, P=0.0003; Figure A); 8 of the 11 deaths (73%) occurred within the first week of ciprofloxacin exposure. The cause of all 11 deaths was aortic or arterial rupture manifesting as hemopericardium or hemothorax; 2 mice also had hematomas near the mesenteric or renal arteries, and 1 had innominate artery dissection. Mortality was significantly increased in both male and female vEDS mice exposed to ciprofloxacin compared to same-sex controls (P=0.02 and P=0.006, respectively). Ascending or descending thoracic aortic dissection was present in 28% (7/25) of ciprofloxacin-treated vEDS mice, but in none of the 24 vehicle-treated vEDS mice (P=0.005) or littermate controls. Compared to aortic tissue from vehicle-treated vEDS mice, tissue from ciprofloxacin-treated vEDS mice exhibited decreased collagen content (P<0.001; Figure B), decreased LOX (P<0.001), and increased macrophage infiltration (P<0.001).
Conclusions: In a mouse model of vEDS, ciprofloxacin exposure resulted in aortic inflammation, collagen disruption, reduced LOX, and increased risk of fatal dissection and rupture of the thoracic aorta and branch arteries. These novel translational findings strongly support recommendations to avoid fluoroquinolones in patients with vEDS.
Compared to controls, vEDS mice exposed to ciprofloxacin exhibited significantly reduced (A) survival and (B) ascending aortic collagen content.
Back to 2026 Abstracts
