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Updated: Aug 18, 2025
Murine Aortic Crush Injury: An Efficient In Vivo Model of Smooth Muscle Cell Proliferation and Endothelial Function
Published on: June 11, 2017
Ciprofloxacin exacerbates dysfunction of smooth muscle cells in a microphysiological model of thoracic aortic
Bitao Xiang1,2, Mieradilijiang Abudupataer1,2, Gang Liu1,2
1Department of Cardiac Surgery, and.
Abstract:
Ciprofloxacin use may be associated with adverse aortic events. However, the mechanism underlying the effect of ciprofloxacin on the progression of thoracic aortic aneurysm (TAA) is not well understood. Using an in vitro microphysiological model, we treated human aortic smooth muscle cells (HASMCs) derived from patients with bicuspid aortic valve- or tricuspid aortic valve-associated (BAV- or TAV-associated) TAAs with ciprofloxacin. TAA C57BL/6 mouse models were utilized to verify the effects of ciprofloxacin exposure. In the microphysiological model, real-time PCR, Western blotting, and RNA sequencing showed that ciprofloxacin exposure was associated with a downregulated contractile phenotype, an upregulated inflammatory reaction, and extracellular matrix (ECM) degradation in the normal HASMCs derived from the nondiseased aorta. Ciprofloxacin induced mitochondrial dysfunction in the HASMCs and further increased apoptosis by activating the ERK1/2 and P38 mitogen-activated protein kinase pathways. These adverse effects appeared to be more severe in the HASMCs derived from BAV- and TAV-associated TAAs than in the normal HASMCs when the ciprofloxacin concentration exceeded 100 μg/mL. In the aortic walls of the TAA-induced mice, ECM degradation and apoptosis were aggravated after ciprofloxacin exposure. Therefore, ciprofloxacin should be used with caution in patients with BAV- or TAV-associated TAAs.
Insights
Ciprofloxacin may worsen thoracic aortic aneurysms (TAAs) by damaging aortic cells and increasing inflammation and matrix degradation. Caution is advised for patients with bicuspid or tricuspid aortic valve-associated TAAs.
Area of Science:
- Cardiovascular Research
- Pharmacology
- Cell Biology
Background:
- Ciprofloxacin use is linked to aortic events, but its mechanism in thoracic aortic aneurysm (TAA) progression is unclear.
- Understanding ciprofloxacin's cellular effects is crucial for managing TAA patients.
Purpose of the Study:
- To investigate the cellular mechanisms by which ciprofloxacin affects thoracic aortic aneurysm (TAA) progression.
- To evaluate ciprofloxacin's impact on human aortic smooth muscle cells (HASMCs) and TAA mouse models.
Main Methods:
- Utilized an in vitro microphysiological model with HASMCs from normal and TAA patients (bicuspid aortic valve- and tricuspid aortic valve-associated).
- Employed real-time PCR, Western blotting, and RNA sequencing to analyze cellular changes.
- Verified findings in TAA-induced C57BL/6 mouse models.
Main Results:
- Ciprofloxacin downregulated contractile phenotype, upregulated inflammation, and caused extracellular matrix (ECM) degradation in HASMCs.
- Induced mitochondrial dysfunction and apoptosis via ERK1/2 and P38 MAPK pathways.
- Adverse effects were more pronounced in TAA-derived HASMCs above 100 μg/mL ciprofloxacin; ECM degradation and apoptosis were aggravated in mouse models.
Conclusions:
- Ciprofloxacin adversely affects HASMCs, promoting inflammation and ECM degradation, potentially accelerating TAA progression.
- The drug induces mitochondrial dysfunction and apoptosis, with heightened severity in cells from BAV- and TAV-associated TAAs.
- Ciprofloxacin should be used cautiously in patients with BAV- or TAV-associated TAAs due to potential risks.
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