Inhibition of coagulation factor XI attenuates inflammation in myocardial ischemia/reperfusion injury

Abstract Background Increasing evidence suggests that FXI is an attractive target for antithrombotic therapy because it reduces thrombosis without increasing bleeding risk. Patients with decreased levels of are at reduced risk cardiovascular diseases and thromboembolic events. We have already revealed depletion inhibits the vascular coagulation-inflammatory circuit in angiotensin II-induced arterial hypertension. However, effect on cardiac inflammation function ischemia/reperfusion (I/R) injury unknown. Purpose Using FXI-depleted mice to investigate role response post I/R injury. Methods 8–12 weeks old C57BL/6J male were injected intraperitoneally antisense oligonucleotide (FXI ASO) or scrambled controls a period 2 weeks. Then we temporarily ligated left anterior descending (LAD) 45 minutes induce myocardial ischemia, followed by reperfusion 72 hours (ischemia/reperfusion injury, IRI). Myocardial analyzed flow cytometry, real-time PCR, relaxation studies from isolated aortic segment organ chamber chemiluminescence photon counting oxidative burst whole blood. Results ASO treatment hepatic mRNA prolonged activated partial thromboplastin time. Compared mice, blood endothelial dysfunction IRI. control groups, attenuated infiltration CD45+CD11b+ cells, especially LyG-LyChigh monocytes LyG+ neutrophils day 3 Furthermore, expression adhesion molecules pro-inflammatory cytokines, such as Vcam-1, CCL2, IL-6 IL-1b, ischemic myocardium significantly depleted Conclusion Our results suggest Inhibition leads reduction ROS production well attenuation inflammatory influx cells myocardium. This indicates could be potential further Funding Acknowledgement Type funding sources: Public grant(s) – EU funding. Main source(s): TICARDIO project has received European Union's Horizon 2020 research Innovation programme under Marie Skłodowska-Curie grant agreement No 813409.