Reducing Abdominal Aortic Aneurysm Progression by Blocking Neutrophil Extracellular Traps Depends on Thrombus Formation

Nahla Ibrahim; Sonja Bleichert; Johannes Klopf; Gabriel Kurzreiter; Hubert Hayden; Viktoria Knöbl; Tyler Artner; Moritz Krall; Alexander Stiglbauer-Tscholakoff; Rudolf Oehler; Peter Petzelbauer; Albert Busch; Marc A Bailey; Wolf Eilenberg; Christoph Neumayer; Christine Brostjan

doi:10.1016/j.jacbts.2023.11.003

Reducing Abdominal Aortic Aneurysm Progression by Blocking Neutrophil Extracellular Traps Depends on Thrombus Formation

JACC Basic Transl Sci. 2024 Jan 10;9(3):342-360. doi: 10.1016/j.jacbts.2023.11.003. eCollection 2024 Mar.

Authors

Nahla Ibrahim¹, Sonja Bleichert¹, Johannes Klopf¹, Gabriel Kurzreiter¹, Hubert Hayden¹, Viktoria Knöbl¹, Tyler Artner², Moritz Krall¹, Alexander Stiglbauer-Tscholakoff³, Rudolf Oehler⁴, Peter Petzelbauer⁵, Albert Busch⁶, Marc A Bailey^{7

8}, Wolf Eilenberg¹, Christoph Neumayer¹, Christine Brostjan¹

Affiliations

¹ Division of Vascular Surgery, Department of General Surgery, Medical University of Vienna and University Hospital Vienna, Vienna, Austria.
² Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna and University Hospital Vienna, Vienna, Austria.
³ Division of Cardiovascular and Interventional Radiology, Division of Molecular and Gender Imaging, Department of Biomedical Imaging and Image Guided Therapy, Medical University of Vienna and University Hospital Vienna, Vienna, Austria.
⁴ Division of Visceral Surgery, Department of General Surgery, Medical University of Vienna and University Hospital Vienna, Vienna, Austria.
⁵ Skin and Endothelium Research Division, Department of Dermatology, Medical University of Vienna and University Hospital Vienna, Vienna, Austria.
⁶ Department for Visceral, Thoracic and Vascular Surgery, Technical University of Dresden and University Hospital Carl-Gustav Carus, Dresden, Germany.
⁷ Leeds Institute for Cardiovascular and Metabolic Medicine, School of Medicine, University of Leeds, Leeds, United Kingdom.
⁸ Leeds Vascular Institute, Leeds General Infirmary, Leeds, United Kingdom.

Abstract

Neutrophil extracellular traps (NETs) are implicated in the pathogenesis of abdominal aortic aneurysm (AAA), located in adventitia and intraluminal thrombus. We compared the therapeutic potential of targeting upstream or downstream effector molecules of NET formation in 2 murine AAA models based on angiotensin II or peri-adventitial elastase application. In both models, NETs were detected in formed aneurysms at treatment start. Although NET inhibitors failed in the elastase model, they prevented progression of angiotensin II-induced aneurysms with thrombus, which resembles established human disease (including thrombus development). Blockade of upstream NET mediators was more effective than interference with downstream NET molecules.

Keywords: abdominal aortic aneurysm; mouse model; neutrophil extracellular trap; thrombus.