Abstract
Purpose: Factor Xa inhibitors are anticoagulants to reduce in stroke and other thromboembolic events. Fondaparinux (FDP) is an approved indirect factor Xa inhibitor to prevent venous thromboembolism. It is known that the proliferation of cardiac fibroblasts leads the fibrosis of coronary vessels, which are deeply associated with the progression of coronary atherosclerosis, and cardiac remodeling to cause heart failure in clinical settings. However, the effect of FDP in cardiac fibroblasts for the development of atherosclerosis and cardiac remodeling is still remaining unclear. Therefore, we aim to evaluate the functional role of FDP in mouse cardiac fibroblasts stimulated by hydrogen peroxide (H2O2). Materials and methods: Confluent fibroblasts were pretreated with or without FDP (0.34 μg/ml) for 6 hours, and then stimulated by H2O2 in various times. Reactive oxygen species (ROS) were measured by DCFDA method. Cell proliferation was measured by MTT assay after 12 and 24 hours of H2O2 stimulation (25 μM). Interleukin (IL)-6, tumor necrosis factor (TNF)-α, and tissue growth factor (TGF)-β productions were evaluated by ELISA after 12, 24 and 48 hours of H2O2 stimulation (25 μM), respectively. Results: H2O2 stimulation by itself induced excessive ROS production and cell proliferation in mouse cardiac fibroblast. H2O2 (25 mM) induced cell proliferation was significantly decreased in FDP-pretreated cardiac fibroblasts compared to cells without FDP (86% decrease in 24 hours). Although H2O2 had no effect in TNF-α and TGF-β production, IL-6 production was significantly enhanced by FDP pretreatment (84% increase in 48 hours). Conclusion: These data suggest that the pleiotropic effects of factor Xa inhibitor may provide favorable effects on cardiovascular disease prevention, at least part of in vitro model.
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