Abstract 13846: Factor Xa Inhibition Prevents Cardiac Remodeling Induced by Intermittent Hypoxia in Sleep Apnea Model Mice
Introduction: We have reported that intermittent hypoxia (IH) relevant to sleep apnea increases oxidative stress causing vascular remodeling and heart failure. The serine protease factor Xa in the coagulation cascade elicits inflammatory responses in endothelial cells.
Hypothesis: We hypothesize that rivaroxaban might attenuate cardiac remodeling induced by IH in sleep apnea model mice.
Methods: Male C57BL/6J mice at 8 weeks of age were exposed to IH (repeated cycles of 1.5 minute of 5% oxygen followed by 5 minutes of 21% oxygen) for 56 days with/without treatment by rivaroxaban (1.2 g riv./kg chow). After echocardiography, heart was examined by light and electron microscopy, immunohistochemistry, and RT-PCR. HPAECs were cultured under hypoxic conditions (37%, 1% O2, 5% CO2) with/without rivaroxaban (1 μM).
Results: IH caused cardiac remodeling (Figure), associated with both systolic and diastolic dysfunction compared with those of normoxia (IH vehicle vs. Normoxia; EF: 51.8% vs. 59.4% and E/e’: 29.4 vs. 22.3), which were attenuated by rivaroxaban (EF: 55.8%, E/e’: 24.6). In right atrial myocardium, IH caused endothelial cell degeneration, dissociation of intercalated discs, vacuolar formation and loss of ANP specific granules. Furthermore, 4-hydroxy-2-nonenal protein adducts and the expression of protease-activated receptor-1 (PAR-1) and NF-kB mRNA were increased by IH. Treatment with rivaroxaban significantly suppressed PAR-1 and NF-kB mRNA expression, increased ANP granules and reduced perivascular fibrosis, preventing cardiac remodeling due to IH.
Conclusions: Rivaroxaban may attenuate atrial and ventricular remodeling induced by IH at least partly through its anti-inflammatory effect in sleep apnea model mice.
Author Disclosures: F. Yoshimura: None. S. Tanikawa: None. S. Hosako: None. R. Kato: None. Y. Ijiri: None. Y. Izumi: None. M. Yoshiyama: None. T. Hayashi: None.
- © 2015 by American Heart Association, Inc.