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Ciprofloxacin accelerates aortic enlargement and promotes dissection and rupture in Marfan mice
Scott A LeMaire1, Lin Zhang2, Nicholas S Zhang3
1Division of Cardiothoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Tex; Department of Cardiovascular Surgery, Texas Heart Institute, Houston, Tex; Cardiovascular Research Institute, Baylor College of Medicine, Houston, Tex.
Objective:
Aortic aneurysm and dissection are major life-threatening complications of Marfan syndrome. Avoiding factors that promote aortic damage is critical in managing the care of these patients. Findings from clinical and animal studies raise concerns regarding fluoroquinolone use in patients at risk for aortic aneurysm and dissection. Therefore, we examined the effects of ciprofloxacin on aortic aneurysm and dissection development in Marfan mice.
Methods:
Eight-week-old Marfan mice (Fbn1C1041G/+) were given ciprofloxacin (100 mg/kg/d; n = 51) or vehicle (n = 59) for 4 weeks. Mice were monitored for 16 weeks. Aortic diameters were measured by using ultrasonography, and aortic structure was examined by using histopathologic and immunostaining analyses.
Results:
Vehicle-treated Fbn1C1041G/+ mice showed progressive aortic enlargement, with aortic rupture occurring in 5% of these mice. Compared with vehicle-treated Fbn1C1041G/+ mice, ciprofloxacin-treated Fbn1C1041G/+ mice showed accelerated aortic enlargement (P = .01) and increased incidences of aortic dissection (25% vs 47%, P = .03) and rupture (5% vs 25%, P = .005). Furthermore, ciprofloxacin-treated Fbn1C1041G/+ mice had higher levels of elastic fiber fragmentation, matrix metalloproteinase expression, and apoptosis than did vehicle-treated Fbn1C1041G/+ mice.
Conclusions:
Ciprofloxacin accelerates aortic root enlargement and increases the incidence of aortic dissection and rupture in Marfan mice, partially by suppressing lysyl oxidase expression and further compromising the inherited defect in aortic elastic fibers. Our findings substantiate that ciprofloxacin should be avoided in patients with Marfan syndrome.
Insights
Ciprofloxacin significantly worsens aortic aneurysm and dissection in Marfan mice by accelerating aortic enlargement and increasing rupture rates. These findings indicate fluoroquinolones should be avoided in Marfan syndrome patients.
Area of Science:
- Cardiovascular Research
- Genetics and Disease
- Pharmacology
Background:
- Marfan syndrome is a genetic disorder associated with life-threatening aortic complications, including aneurysm and dissection.
- Identifying factors that exacerbate aortic damage is crucial for managing Marfan syndrome patients.
- Previous studies suggest potential risks of fluoroquinolone use in individuals susceptible to aortic diseases.
Purpose of the Study:
- To investigate the impact of ciprofloxacin on the development of aortic aneurysm and dissection in a mouse model of Marfan syndrome.
- To determine if ciprofloxacin use alters the progression of aortic pathology in genetically predisposed individuals.
Main Methods:
- Marfan mice (Fbn1C1041G/+) were administered ciprofloxacin or vehicle for four weeks.
- Aortic dimensions were monitored using ultrasonography over a 16-week period.
- Histopathological and immunostaining analyses were performed to assess aortic structural integrity.
Main Results:
- Ciprofloxacin treatment led to accelerated aortic enlargement and a higher incidence of aortic dissection and rupture compared to vehicle-treated mice.
- Mice treated with ciprofloxacin exhibited increased elastic fiber fragmentation, matrix metalloproteinase expression, and apoptosis in the aorta.
- Vehicle-treated Marfan mice showed progressive aortic enlargement, with a 5% rate of aortic rupture.
Conclusions:
- Ciprofloxacin exacerbates aortic root enlargement and increases the risk of dissection and rupture in Marfan mice.
- The drug's effects are partly attributed to suppressed lysyl oxidase expression, worsening inherent aortic elastic fiber defects.
- These findings strongly support avoiding ciprofloxacin in patients diagnosed with Marfan syndrome.
