Levofloxacin promotes extracellular matrix remodeling and apoptosis of heart valve interstitial cells
Abstract
BACKGROUND: Fluoroquinolones (FQs) have been associated with an increased risk of heart valve regurgitation, yet the cellular mechanisms underlying this association remain unclear. Although the effects of fluoroquinolones on cardiac valvular interstitial cells have been explored in experimental models, the specific impacts and mechanisms of levofloxacin on heart valve interstitial cells remain insufficiently understood.
MATERIALS AND METHODS: Aortic interstitial cells (AICs), mitral interstitial cells (MICs), and tricuspid interstitial cells (TICs) were extracted through collagenase digestion. The isolated cells were divided into the intervention group (treated with 20 μg/mL levofloxacin) and control group. The expression of matrix metalloproteinases (MMPs), collagen, and elastin was quantified by Western blot (WB). The impact of levofloxacin on cell apoptosis was explored using flow cytometry.
RESULTS: The expression level of MMPs, which contribute to collagen degradation, was upregulated in AICs, MICs, and TICs treated with levofloxacin. Elastin and collagen, the key components of the extracellular matrix (ECM) of cardiac valve cells, were decreased in AICs and TICs, whereas no significant changes were observed in MICs following levofloxacin treatment. Moreover, prolonged levofloxacin exposure significantly enhanced apoptosis in MICs, while a pro-apoptotic trend was observed in AICs and TICs.
CONCLUSIONS: Levofloxacin promoted extracellular matrix remodeling by modulating…
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