Resolution of Inflammation Through the Lipoxin and ALX/FPR2 Receptor Pathway Protects Against Abdominal Aortic Aneurysms

Marcelo H. Petri, MD, PhD; Silke Thul, PhD; Teodora Andonova, MSc; Moritz Lindquist-Liljeqvist, MD; Hong Jin, MD, PhD; Nikolaos-Taxiarchis Skenteris, MSc; Hildur Arnardottir, PhD; Lars Maegdefessel, MD, PhD; Kenneth Caidahl, MD, PhD; Mauro Perretti, PhD; Joy Roy, MD, PhD; Magnus Bäck, MD, PhD

JACC: Basic to Translational Science (Dec 2018)

Resolution of Inflammation Through the Lipoxin and ALX/FPR2 Receptor Pathway Protects Against Abdominal Aortic Aneurysms

Marcelo H. Petri, MD, PhD,
Silke Thul, PhD,
Teodora Andonova, MSc,
Moritz Lindquist-Liljeqvist, MD,
Hong Jin, MD, PhD,
Nikolaos-Taxiarchis Skenteris, MSc,
Hildur Arnardottir, PhD,
Lars Maegdefessel, MD, PhD,
Kenneth Caidahl, MD, PhD,
Mauro Perretti, PhD,
Joy Roy, MD, PhD,
Magnus Bäck, MD, PhD

Affiliations

Marcelo H. Petri, MD, PhD: Department of Medicine, Karolinska Institutet, Stockholm, Sweden
Silke Thul, PhD: Department of Medicine, Karolinska Institutet, Stockholm, Sweden
Teodora Andonova, MSc: Department of Medicine, Karolinska Institutet, Stockholm, Sweden
Moritz Lindquist-Liljeqvist, MD: Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
Hong Jin, MD, PhD: Department of Medicine, Karolinska Institutet, Stockholm, Sweden
Nikolaos-Taxiarchis Skenteris, MSc: Department of Medicine, Karolinska Institutet, Stockholm, Sweden
Hildur Arnardottir, PhD: Department of Medicine, Karolinska Institutet, Stockholm, Sweden
Lars Maegdefessel, MD, PhD: Department of Medicine, Karolinska Institutet, Stockholm, Sweden
Kenneth Caidahl, MD, PhD: Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Department of Molecular and Clinical Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
Mauro Perretti, PhD: William Harvey Research Institute, Barts and London School of Medicine, Centre for Inflammation and Therapeutic Innovation, Queen Mary University of London, London, United Kingdom
Joy Roy, MD, PhD: Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Theme Heart and Vessels, Division of Valvular and Coronary Disease, Karolinska University Hospital, Stockholm, Sweden
Magnus Bäck, MD, PhD: Department of Medicine, Karolinska Institutet, Stockholm, Sweden; Theme Heart and Vessels, Division of Valvular and Coronary Disease, Karolinska University Hospital, Stockholm, Sweden; Address for correspondence: Dr. Magnus Bäck, Translational Cardiology, S1:02, Karolinska University Hospital, 171 76 Stockholm, Sweden.

Journal volume & issue: Vol. 3, no. 6
pp. 719 – 727

Abstract

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Summary: An abdominal aortic aneurysm (AAA) is a progressive aortic dilation that may lead to rupture, which is usually lethal. This study identifies the state of failure in the resolution of inflammation by means of decreased expression of the pro-resolving receptor A lipoxin/formyl peptide receptor 2 (ALX/FPR2) in the adventitia of human AAA lesions. Mimicking this condition by genetic deletion of the murine ALX/FPR2 ortholog in hyperlipidemic mice exacerbated the aortic dilation induced by angiotensin II infusion, associated with decreased vascular collagen and increased inflammation. The authors also identified key roles of lipoxin formation through 12/15-lipoxygenase and neutrophil p38 mitogen-activated protein kinase. In conclusion, this study established pro-resolving signaling by means of the ALX/FPR2 receptor in aneurysms and vascular inflammation. Key Words: abdominal aortic aneurysms, cardiovascular disease, eicosanoids, inflammation, lipoxygenase

Published in JACC: Basic to Translational Science

ISSN: 2452-302X (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Specialties of internal medicine: Diseases of the circulatory (Cardiovascular) system
Website: https://www.journals.elsevier.com/jacc-basic-to-translational-science/

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