Factor Xa inhibition by rivaroxaban attenuates cardiac remodeling due to intermittent hypoxia.

Patients with obstructive sleep apnea (OSA) have a high prevalence of atrial fibrillation (AF). Rivaroxaban, a coagulation factor Xa inhibitor, has recently been reported to show pleiotropic effects. This study investigated the influence of rivaroxaban on cardiac remodeling caused by intermittent hypoxia (IH). Male C57BL/6J mice were exposed to IH (repeated cycles of 5% oxygen for 1.5 min followed by 21% oxygen for 5 min) for 28 days with/without rivaroxaban (12 mg/kg/day) or FSLLRY, a protease-activated receptor (PAR)-2 antagonist (10 µg/kg/day). IH caused endothelial cell degeneration in the small arteries of the right atrial myocardium and increased the level of %fibrosis and 4-hydroxy-2-nonenal protein adducts in the left ventricular myocardium. IH also increased the expression of PAR-2 as well as the phosphorylation of extracellular signal-regulated kinase (ERK)-1/2 and nuclear factor-kappa B (NF-κB) were increased in human cardiac microvascular endothelial cells. However, rivaroxaban and FSLLRY significantly suppressed these changes. These findings demonstrate that rivaroxaban attenuates both atrial and ventricular remodeling induced by IH through the prevention of oxidative stress and fibrosis by suppressing the activation of ERK and NF-κB pathways via PAR-2. Treatment with rivaroxaban could potentially become a novel therapeutic strategy for cardiac remodeling in patients with OSA and AF.

Insight into the mechanism of end-of-day far-red light (EODFR)-induced shade avoidance responses in Arabidopsis thaliana.

Shade avoidance responses are changes in plant architecture to reduce the part of a body that is in the shade in natural habitats. The most common warning signal that induces shade avoidance responses is reduction of red/far-red light ratio perceived by phytochromes. A pair of basic helix-loop-helix transcription factors, named PHYTOCHROME-INTERACTING FACTOR 4 (PIF4) and PIF5, is crucially involved in the shade avoidance-induced hypocotyl elongation in Arabidopsis thaliana. It has been recently reported that PIF7 also plays a role in this event. Here, we examined the involvement of these PIFs in end-of-day far-red light (EODFR) responses under light and dark cycle conditions. It was shown that PIF7 played a predominant role in the EODFR-dependent hypocotyl elongation. We propose the mechanism by which PIF7 together with PIF4 and PIF5 coordinately transcribes a set of downstream genes to promote elongation of hypocotyls in response to the EODFR treatment.