Neutrophil-activating Peptide 2 as a Novel modulator of fibrin clot properties in patients with atrial fibrillation

Introduction: Neutrophil-activating peptide 2 (NAP-2, CXCL7), a platelet-derived neutrophil chemoattractant, is involved in inflammation. We investigated associations between NAP-2 levels, neutrophil extracellular traps (NETs) formation, and fibrin clot properties in atrial fibrillation (AF). Materials and Methods: We recruited 237 consecutive patients with AF (mean age, 68±11 years; median CHA2DS2VASc score of 3 [2-4]) and 30 apparently healthy controls. Plasma NAP-2 concentrations were measured, along with plasma fibrin clot permeability (Ks) and clot lysis time (CLT), thrombin generation, citrullinated histone H3 (citH3), as a marker of NETs formation, and 3-nitrotyrosine reflecting oxidative stress. Results: NAP-2 levels were 89% higher in AF patients than in controls (626 [448-796] vs. 331 [226-430] ng/ml; p2DS2-VASc score, or the AF manifestation. Patients with NAP-2 in the top quartile (>796 ng/ml) were characterized by higher neutrophil count (+31.7%), fibrinogen (+20.8%), citH3 (+86%), and 3-nitrotyrosine (+111%) levels, along with 20.2% reduced Ks and 8.4% prolonged CLT as compared to the remaining subjects (all ps. Conclusions: Elevated NAP-2, associated with increased oxidative stress, has been identified as a novel modulator of prothrombotic plasma fibrin clot properties in patients with AF.