OC 70.5 - Coagulation factor XI contributes to the infarct size and inflammation in myocardial ischemia/reperfusion injury

Background: Coagulation factor XI (FXI) is proven as a potential target for antithrombotic therapy in many animal and human studies. FXI deficiency patients are at a lower risk of cardiovascular diseases and thromboembolic events. Depletion of FXI inhibits the vascular coagulation-inflammatory circuit and ameliorates end-stage organ damage in angiotensin II-induced arterial hypertension mouse model. However, the effect of FXI depletion on cardiac inflammation in ischemia/reperfusion (I/R) injury is unknown.

Aims: To investigate the role of FXI-depletion in the inflammatory response in cardiac I/R injury.

Methods: 8-12 weeks old C57BL/6J male mice were injected intraperitoneally with FXI antisense oligonucleotide (FXI ASO) or scrambled ASO. The left anterior descending (LAD) was temporarily ligated for 45 minutes to induce myocardial ischemia, followed by 72-hour reperfusion (ischemia/reperfusion injury). Myocardial inflammation was analyzed by flow cytometry, real-time PCR. Infarct size of heart was assessed by histology.

Results: FXI levels were effectively decreased after repetitive injections of FXI ASO. Compared to scrambled ASO control group, depletion of FXI attenuated cardiac infiltration of CD45+CD11b+ myelomonocytic cells, especially LyG+ neutrophils and LyG-LyChigh monocytes. The expression levels of pro-inflammatory cytokines IL-6, IL-1beta and TNFa in ischemic myocardium were significantly decreased after inhibition of FXI. Furthermore, the infarct size was decreased in FXI ASO treatment group.

Conclusion(s): Our results suggest that inhibition of FXI attenuated cardiac inflammatory response and infracted size in I/R injury, indicating that FXI may play a role in progression of cardiac I/R injury.