Atrial Fibrillation Mice Exhibit Abnormal Coagulation, Inflammatory, and NETosis Markers
Michael Wu1, Junxiang Yin1, Michael Waters2
1Icahn School of Medicine, 2Mount Sinai School of Medicine
Objective:
The objective of this study is to characterize a novel, spontaneous atrial fibrillation mouse model and determining its suitability to study AF-stroke comorbidity.
Background:
Atrial fibrillation (AF) makes it 5 times more likely for an individual to have a stroke. One possible mechanism contributing to the propagation of atrial fibrillation and thromboembolic sequelae is the presence of neutrophil extracellular traps (NETs) as an abnormal blood constituent. NETs in circulation are upregulated in AF patients and implicated in increased endovascular dysfunction and hypercoagulability – two important factors for thrombogenesis. However, the exact role of NETs in AF-induced coagulopathy remains unknown. To study this, we will be using a novel mouse model for atrial cardiomyopathy and spontaneous atrial fibrillation first generated by Hulsurkar et al by knocking down liver kinase B1 in the atria of mice (LKB1-aKD).
Design/Methods:
LKB1-aKD mice were generated by introducing LKB1-floxed mice with AAV9 containing a plasmid for atrial-specific CRE expression. These mice were evaluated using EKG to confirm atrial fibrillation. AF mice were sacrificed at 6-months, and plasma was collected for evaluation of coagulation markers, inflammatory markers, and NET markers. Cardiac tissue was also collected and evaluated histologically for structural and pathological changes.
Results:
AF mice displayed paroxysms of irregularly-irregular dysrhythmia as well as possible atrial flutter which were absent in littermate controls. AF mice had significantly elevated levels of plasma coagulation factors, and also intra-atrial thrombus deposition relative to littermate controls. These AF mice additionally displayed significantly elevated levels of plasma IL-6, IL1-β, TNF-α, and neutrophil elastase.
Conclusions:
Our data is the first to demonstrate that LKB1-aKD mice has significantly elevated levels of plasma coagulation, inflammatory, and NET markers. This study provides evidence for the potential use of LKB1-aKD mice as an effective model for studying AF-stroke comorbidity and the potential role of NETs in worse stroke outcomes in AF.
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