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May 24-25, 2018
London, UK
Vascular Surgery 2018
3
rd
Edition of World Congress & Exhibition on
Vascular Surgery
Journal of Vascular and Endovascular Therapy
ISSN: 2573-4482
N
eutrophil extracellular traps (NETs) have been implicated
in the pathogenesis of abdominal aortic aneurysms
(AAAs). NET formation involves histone modifications such
as citrullination allowing for DNA decondensation and DNA
release into extracellular space. NETs have been detected in
the adventitia and intraluminal thrombus (ILT) of AAAs and
the associated proteins have been proposed to promote the
inflammatory reaction that drives aneurysm development. Our
study has addressed the notion that NET components might
serve as AAA biomarkers or novel targets of AAA therapy.
Parametersof neutrophil activationaswell asNETformationwere
determined in blood and tissue samples collected from 40 AAA
patients (scheduled for surgical repair) and 40 healthy controls
matched for age, sex, body mass index and smoking habit.
Neutrophil and NET components were determined by ELISA in
patient plasma or conditioned medium of resected tissue. NETs
were visualised in aortic wall and ILT by immunofluorescence
microscopy. In a model of AAA formation based on angiotensin
II administration to ApoE null mice, inhibition of NET formation
was tested by applying a citrullination blocker. Among the
tested parameters of neutrophil activation and NET formation,
citrullinated histone H3 was found to be significantly increased
in blood (median 362 vs. 309 ng/ml p=0.004) and aortic tissue
(50.9 vs. 3.7 ng/mg p=0.001) of AAA patients compared to
healthy controls. Furthermore, NETs were highly prevalent in the
intraluminal thrombus (corresponding to 642.3 ng citrullinated
histone H3 per mg ILT). Plasma levels of citrullinated histone H3
decreased significantly after surgical repair. In vivo application
of a citrullination inhibitor significantly reduced the capacity
of mouse neutrophils to undergo NET formation. Furthermore,
when aneurysm formation was initiated by angiotensin II
application, disease progression was prevented in mice
treated with the NET inhibitor (N=5) as compared to controls
(N=5; p=0.014). Histone citrullination which occurs during the
formation of neutrophil extracellular traps was revealed as a
biomarker of AAA formation and a potential therapeutic target
to control aneurysm progression in established disease (as
would be required for clinical application).
Recent Publications
1. Eilenberg W, Stojkovic S, Piechota-Polanczyk A, Kaun
C, Rauscher S, Groger M, et al. Neutrophil Gelatinase-
Associated Lipocalin (NGAL) is Associated with
Symptomatic Carotid Atherosclerosis and Drives Pro-
inflammatory State In Vitro. Eur J Vasc Endovasc Surg.
2016 May;51(5):623-31. PubMed PMID: 26947538.
Epub 2016/03/08.
2. Eilenberg W, Stojkovic S, Kaider A, Kozakowski N,
Domenig CM, Burghuber C, et al. NGAL and MMP-9/
NGAL as biomarkers of plaque vulnerability and targets
of statins in patients with carotid atherosclerosis. Clin
Chem Lab Med. 2017 Jun 26. PubMed PMID: 28672747.
Epub 2017/07/05. eng.
3. W. Eilenberg, S. Stojkovic, A. Piechota-Polanczyk, A.
Kaider, N. Kozakowski, W. Weninger, J. Nanobachvili,
J. Wojta, I. Huk, S. Demyanets, C. Neumayer Neutrophil
Gelatinase Associated Lipocalin (NGAL) is elevated in
type 2 diabetics with carotid artery stenosis and reduced
under metformin treatment Cardiovascular Diabetology
(2017) 8;16 (1):98
Biography
Wolf Eilenberg is a surgeon at the Department of Surgery at the Medical
University Vienna. His research focus and expertise involves the role of
neutrophils in carotid atherosclerotic disease and biomarkers of vulnerable
carotid plaque. During the last few years, his primary interest was NGAL
Histone citrullination of neutrophil extracellular traps is a
novel biomarker and target to inhibit progression of abdominal
aortic aneurysms
Wolf Eilenberg, Christoph Neumayer, Branislav Zagrapan, Luca Martelanz, Ma-
rie-Therese Grasl, Alexandros Potolidis, Paimann Nawrozi, Patrick Kirchweger,
Christoph Domenig, Ihor Huk
and
Christine Brostjan
Medical University of Vienna, Austria
Wolf Eilenberg et al., J Vasc Endovasc Therapy 2018, Volume 3
DOI: 10.21767/2573-4482-C1-002