PMID- 33571683
OWN - NLM
STAT- MEDLINE
DCOM- 20210806
LR  - 20211204
IS  - 1878-1810 (Electronic)
IS  - 1878-1810 (Linking)
VI  - 233
DP  - 2021 Jul
TI  - Histone citrullination as a novel biomarker and target to inhibit progression of 
      abdominal aortic aneurysms.
PG  - 32-46
LID - S1931-5244(21)00026-8 [pii]
LID - 10.1016/j.trsl.2021.02.003 [doi]
AB  - Neutrophil extracellular traps (NETs) have been implicated in the pathogenesis of 
      abdominal aortic aneurysms (AAAs). This study has addressed the notion that NET 
      components might serve as AAA biomarkers or novel targets of AAA therapy. Thus, 
      parameters of neutrophil activation and NET formation were measured in plasma. 
      Their diagnostic marker value was explored in 41 AAA patients and 38 healthy 
      controls. The NET parameter citrullinated histone H3 (citH3) was then validated 
      in 63 AAA patients and 63 controls matched for cardiovascular disease. The 
      prognostic marker potential was investigated in 54 observation periods of AAA 
      growth over 6 months. NETs were further assessed in conditioned medium and 
      sections of aortic tissue. CitH3 was found to be increased in blood (median 362 
      vs 304 ng/mL, P = 0.004) and aortic tissue (50 vs 1.5 ng/mg, P < 0.001) of AAA 
      patients compared to healthy controls and accumulated in the intraluminal 
      thrombus (629 ng/mg). The diagnostic potential of citH3 ranged at 0.705 area 
      under the ROC curve (AUROC) and was validated with the independent sample set. 
      Furthermore, plasma citH3 predicted AAA growth over the next 6 months (AUROC: 
      0.707, P = 0.015) and dropped significantly after surgical aneurysm repair. In an 
      angiotensin II - based mouse model of experimental AAA, an inhibitor of histone 
      citrullination was applied to block NET formation and AAA progression. Of note, 
      further growth of an established aneurysm was prevented in mice treated with the 
      NET inhibitor (P = 0.040). In conclusion, histone citrullination represents a 
      promising AAA biomarker and potential therapeutic target to control disease 
      progression.
CI  - Copyright (c) 2021 The Author(s). Published by Elsevier Inc. All rights reserved.
FAU - Eilenberg, Wolf
AU  - Eilenberg W
AD  - Department of General Surgery: Division of Vascular Surgery, Medical University 
      of Vienna, Vienna, Austria.
FAU - Zagrapan, Branislav
AU  - Zagrapan B
AD  - Department of General Surgery: Division of Vascular Surgery, Medical University 
      of Vienna, Vienna, Austria.
FAU - Bleichert, Sonja
AU  - Bleichert S
AD  - Department of General Surgery: Division of Vascular Surgery, Medical University 
      of Vienna, Vienna, Austria.
FAU - Ibrahim, Nahla
AU  - Ibrahim N
AD  - Department of General Surgery: Division of Vascular Surgery, Medical University 
      of Vienna, Vienna, Austria.
FAU - Knobl, Viktoria
AU  - Knobl V
AD  - Department of General Surgery: Division of Vascular Surgery, Medical University 
      of Vienna, Vienna, Austria.
FAU - Brandau, Annika
AU  - Brandau A
AD  - Department of General Surgery: Division of Vascular Surgery, Medical University 
      of Vienna, Vienna, Austria.
FAU - Martelanz, Luca
AU  - Martelanz L
AD  - Department of General Surgery: Division of Vascular Surgery, Medical University 
      of Vienna, Vienna, Austria.
FAU - Grasl, Marie-Therese
AU  - Grasl MT
AD  - Department of General Surgery: Division of Vascular Surgery, Medical University 
      of Vienna, Vienna, Austria.
FAU - Hayden, Hubert
AU  - Hayden H
AD  - Department of General Surgery: Division of Vascular Surgery, Medical University 
      of Vienna, Vienna, Austria.
FAU - Nawrozi, Paimann
AU  - Nawrozi P
AD  - Department of General Surgery: Division of Vascular Surgery, Medical University 
      of Vienna, Vienna, Austria.
FAU - Rajic, Renata
AU  - Rajic R
AD  - Department of General Surgery: Division of Vascular Surgery, Medical University 
      of Vienna, Vienna, Austria.
FAU - Hausler, Charlotte
AU  - Hausler C
AD  - Department of General Surgery: Division of Vascular Surgery, Medical University 
      of Vienna, Vienna, Austria.
FAU - Potolidis, Alexandros
AU  - Potolidis A
AD  - Department of General Surgery: Division of Vascular Surgery, Medical University 
      of Vienna, Vienna, Austria.
FAU - Schirwani, Nawa
AU  - Schirwani N
AD  - Department of General Surgery: Division of Vascular Surgery, Medical University 
      of Vienna, Vienna, Austria.
FAU - Scheuba, Andreas
AU  - Scheuba A
AD  - Department of General Surgery: Division of Vascular Surgery, Medical University 
      of Vienna, Vienna, Austria.
FAU - Klopf, Johannes
AU  - Klopf J
AD  - Department of General Surgery: Division of Vascular Surgery, Medical University 
      of Vienna, Vienna, Austria.
FAU - Teubenbacher, Peter
AU  - Teubenbacher P
AD  - Department of General Surgery: Division of Vascular Surgery, Medical University 
      of Vienna, Vienna, Austria.
FAU - Weigl, Markus P
AU  - Weigl MP
AD  - Department of General Surgery: Division of Vascular Surgery, Medical University 
      of Vienna, Vienna, Austria.
FAU - Kirchweger, Patrick
AU  - Kirchweger P
AD  - Department of General Surgery: Division of Vascular Surgery, Medical University 
      of Vienna, Vienna, Austria.
FAU - Beitzke, Dietrich
AU  - Beitzke D
AD  - Department of Biomedical Imaging and Image Guided Therapy: Division of 
      Cardiovascular and Interventional Radiology; Division of Molecular and Gender 
      Imaging, Medical University of Vienna, Vienna, Austria.
FAU - Stiglbauer-Tscholakoff, Alexander
AU  - Stiglbauer-Tscholakoff A
AD  - Department of Biomedical Imaging and Image Guided Therapy: Division of 
      Cardiovascular and Interventional Radiology; Division of Molecular and Gender 
      Imaging, Medical University of Vienna, Vienna, Austria.
FAU - Panzenbock, Adelheid
AU  - Panzenbock A
AD  - Department of Internal Medicine II: Division of Cardiology, Medical University of 
      Vienna, Vienna, Austria.
FAU - Lang, Irene
AU  - Lang I
AD  - Department of Internal Medicine II: Division of Cardiology, Medical University of 
      Vienna, Vienna, Austria.
FAU - Mauracher, Lisa-Marie
AU  - Mauracher LM
AD  - Department of Internal Medicine I: Clinical Division of Haematology and 
      Haemostaseology, Medical University of Vienna, Vienna, Austria.
FAU - Hell, Lena
AU  - Hell L
AD  - Department of Internal Medicine I: Clinical Division of Haematology and 
      Haemostaseology, Medical University of Vienna, Vienna, Austria.
FAU - Pabinger, Ingrid
AU  - Pabinger I
AD  - Department of Internal Medicine I: Clinical Division of Haematology and 
      Haemostaseology, Medical University of Vienna, Vienna, Austria.
FAU - Bailey, Marc A
AU  - Bailey MA
AD  - Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, 
      Faculty of Medicine and Health, Leeds, United Kingdom; Leeds Vascular Institute, 
      Leeds General Infirmary, Leeds, United Kingdom.
FAU - Scott, D Julian A
AU  - Scott DJA
AD  - Leeds Vascular Institute, Leeds General Infirmary, Leeds, United Kingdom; Leeds 
      Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Faculty 
      of Medicine and Health, Leeds, United Kingdom.
FAU - Maegdefessel, Lars
AU  - Maegdefessel L
AD  - Department of Vascular and Endovascular Surgery, Klinikum rechts der Isar, 
      Technical University Munich, Munich, Germany; Molecular Vascular Medicine Group, 
      Centre for Molecular Medicine, Karolinska Institute, Stockholm, Sweden.
FAU - Busch, Albert
AU  - Busch A
AD  - Department of Vascular and Endovascular Surgery, Klinikum rechts der Isar, 
      Technical University Munich, Munich, Germany; Molecular Vascular Medicine Group, 
      Centre for Molecular Medicine, Karolinska Institute, Stockholm, Sweden.
FAU - Huk, Ihor
AU  - Huk I
AD  - Department of General Surgery: Division of Vascular Surgery, Medical University 
      of Vienna, Vienna, Austria.
FAU - Neumayer, Christoph
AU  - Neumayer C
AD  - Department of General Surgery: Division of Vascular Surgery, Medical University 
      of Vienna, Vienna, Austria.
FAU - Brostjan, Christine
AU  - Brostjan C
AD  - Department of General Surgery: Division of Vascular Surgery, Medical University 
      of Vienna, Vienna, Austria. Electronic address: 
      christine.brostjan@meduniwien.ac.at.
LA  - eng
GR  - FS/18/12/33270/BHF_/British Heart Foundation/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210209
PL  - United States
TA  - Transl Res
JT  - Translational research : the journal of laboratory and clinical medicine
JID - 101280339
RN  - 0 (Biomarkers)
RN  - 0 (Histones)
RN  - EC 3.5.3.15 (Padi4 protein, mouse)
RN  - EC 3.5.3.15 (Protein-Arginine Deiminases)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Animals
MH  - Aortic Aneurysm, Abdominal/*metabolism/therapy
MH  - Biomarkers/blood/metabolism
MH  - Case-Control Studies
MH  - *Citrullination/drug effects
MH  - Cohort Studies
MH  - Disease Models, Animal
MH  - Disease Progression
MH  - Extracellular Traps/drug effects/metabolism
MH  - Female
MH  - Histone Code/drug effects
MH  - Histones/blood/*metabolism
MH  - Humans
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout, ApoE
MH  - Middle Aged
MH  - Neutrophils/drug effects/metabolism
MH  - Prognosis
MH  - Protein-Arginine Deiminases/antagonists & inhibitors
MH  - Translational Research, Biomedical
EDAT- 2021/02/12 06:00
MHDA- 2021/08/07 06:00
CRDT- 2021/02/11 20:11
PHST- 2020/11/29 00:00 [received]
PHST- 2021/01/31 00:00 [revised]
PHST- 2021/02/04 00:00 [accepted]
PHST- 2021/02/12 06:00 [pubmed]
PHST- 2021/08/07 06:00 [medline]
PHST- 2021/02/11 20:11 [entrez]
AID - S1931-5244(21)00026-8 [pii]
AID - 10.1016/j.trsl.2021.02.003 [doi]
PST - ppublish
SO  - Transl Res. 2021 Jul;233:32-46. doi: 10.1016/j.trsl.2021.02.003. Epub 2021 Feb 9.