PMID- 37294500 OWN - NLM STAT- Publisher LR - 20230613 IS - 1868-601X (Electronic) IS - 1868-4483 (Print) IS - 1868-4483 (Linking) DP - 2023 Jun 9 TI - Neutrophil-activating Peptide 2 as a Novel Modulator of Fibrin Clot Properties in Patients with Atrial Fibrillation. PG - 1-11 LID - 10.1007/s12975-023-01165-1 [doi] AB - 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). We recruited 237 consecutive patients with AF (mean age, 68 +/- 11 years; median CHA(2)DS(2)VASc score of 3 [2-4]) and 30 apparently healthy controls. Plasma NAP-2 concentrations were measured, along with plasma fibrin clot permeability (K(s)) and clot lysis time (CLT), thrombin generation, citrullinated histone H3 (citH3), as a marker of NETs formation, and 3-nitrotyrosine reflecting oxidative stress. NAP-2 levels were 89% higher in AF patients than in controls (626 [448-796] vs. 331 [226-430] ng/ml; p < 0.0001). NAP-2 levels were not associated with demographics, CHA(2)DS(2)-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 K(s) and 8.4% prolonged CLT as compared to the remaining subjects (all p < 0.05). NAP-2 levels were positively associated with fibrinogen in AF patients (r = 0.41, p = 0.0006) and controls (r = 0.65, p < 0.01), along with citH3 (r = 0.36, p < 0.0001) and 3-nitrotyrosine (r = 0.51, p < 0.0001) in the former group. After adjustment for fibrinogen, higher citH3 (per 1 ng/ml beta = -0.046, 95% CI -0.029; -0.064) and NAP-2 (per 100 ng/ml beta = -0.21, 95% CI -0.14; -0.28) levels were independently associated with reduced K(s). 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. CI - (c) 2023. The Author(s). FAU - Zabczyk, Michal AU - Zabczyk M AD - Department of Thromboembolic Disorders, Institute of Cardiology, Jagiellonian University Medical College, Pradnicka 80, 31-202, Krakow, Poland. AD - Krakow Centre for Medical Research and Technologies, the John Paul II Hospital, Pradnicka 80, Krakow, Poland. FAU - Natorska, Joanna AU - Natorska J AD - Department of Thromboembolic Disorders, Institute of Cardiology, Jagiellonian University Medical College, Pradnicka 80, 31-202, Krakow, Poland. AD - Krakow Centre for Medical Research and Technologies, the John Paul II Hospital, Pradnicka 80, Krakow, Poland. FAU - Matusik, Pawel T AU - Matusik PT AD - Institute of Cardiology, Faculty of Medicine, Jagiellonian University Medical College, Pradnicka 80, Krakow, Poland. AD - Department of Electrocardiology, the John Paul II Hospital, Pradnicka 80, Krakow, Poland. FAU - Molek, Patrycja AU - Molek P AD - Krakow Centre for Medical Research and Technologies, the John Paul II Hospital, Pradnicka 80, Krakow, Poland. FAU - Wojciechowska, Wiktoria AU - Wojciechowska W AD - 1st Department of Cardiology, Interventional Electrocardiology and Arterial Hypertension, Jagiellonian University Medical College, Jakubowskiego 2, Krakow, Poland. FAU - Rajzer, Marek AU - Rajzer M AD - 1st Department of Cardiology, Interventional Electrocardiology and Arterial Hypertension, Jagiellonian University Medical College, Jakubowskiego 2, Krakow, Poland. FAU - Rajtar-Salwa, Renata AU - Rajtar-Salwa R AD - Department of Cardiology and Cardiovascular Interventions, University Hospital, Jakubowskiego 2, Krakow, Poland. FAU - Tokarek, Tomasz AU - Tokarek T AD - Center for Invasive Cardiology, Electrotherapy and Angiology, Kilinskiego 68, Nowy Sacz, Poland. AD - Center for Innovative Medical Education, Jagiellonian University Medical College, Medyczna 9, Krakow, Poland. FAU - Lenart-Migdalska, Aleksandra AU - Lenart-Migdalska A AD - Department of Cardiac and Vascular Diseases, Faculty of Medicine, Institute of Cardiology, Jagiellonian University Medical College, John Paul II Hospital, Pradnicka 80, Krakow, Poland. FAU - Olszowska, Maria AU - Olszowska M AD - Department of Cardiac and Vascular Diseases, Faculty of Medicine, Institute of Cardiology, Jagiellonian University Medical College, John Paul II Hospital, Pradnicka 80, Krakow, Poland. FAU - Undas, Anetta AU - Undas A AUID- ORCID: 0000-0002-0667-8109 AD - Department of Thromboembolic Disorders, Institute of Cardiology, Jagiellonian University Medical College, Pradnicka 80, 31-202, Krakow, Poland. mmundas@cyf-kr.edu.pl. AD - Krakow Centre for Medical Research and Technologies, the John Paul II Hospital, Pradnicka 80, Krakow, Poland. mmundas@cyf-kr.edu.pl. LA - eng GR - N41/DBS/000906/Uniwersytet Jagiellonski Collegium Medicum/ PT - Journal Article DEP - 20230609 PL - United States TA - Transl Stroke Res JT - Translational stroke research JID - 101517297 SB - IM PMC - PMC10250863 OTO - NOTNLM OT - Atrial fibrillation OT - Fibrin clot OT - Neutrophil-activating peptide 2 OT - Oxidative stress COIS- A.U. receives lecture honoraria from Bayer, Pfizer, and Boehringer Ingelheim. P.T.M. received speech honorarium from Boehringer Ingelheim, Polish Cardiac Society 2018 Scientific Grant in cooperation with Berlin-Chemie/Menarini (sponsor of the grant: Berlin-Chemie/Menarini Poland LLC) and participated in educational activities which were supported by Polpharma. EDAT- 2023/06/09 13:42 MHDA- 2023/06/09 13:42 PMCR- 2023/06/09 CRDT- 2023/06/09 11:17 PHST- 2023/03/06 00:00 [received] PHST- 2023/05/30 00:00 [accepted] PHST- 2023/05/23 00:00 [revised] PHST- 2023/06/09 13:42 [medline] PHST- 2023/06/09 13:42 [pubmed] PHST- 2023/06/09 11:17 [entrez] PHST- 2023/06/09 00:00 [pmc-release] AID - 10.1007/s12975-023-01165-1 [pii] AID - 1165 [pii] AID - 10.1007/s12975-023-01165-1 [doi] PST - aheadofprint SO - Transl Stroke Res. 2023 Jun 9:1-11. doi: 10.1007/s12975-023-01165-1.