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

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

doi:10.1016/j.jacbts.2018.08.005

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

JACC Basic Transl Sci. 2018 Dec 31;3(6):719-727. doi: 10.1016/j.jacbts.2018.08.005. eCollection 2018 Dec.

Authors

Affiliations

¹ Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
² Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
³ Department of Molecular and Clinical Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
⁴ William Harvey Research Institute, Barts and London School of Medicine, Centre for Inflammation and Therapeutic Innovation, Queen Mary University of London, London, United Kingdom.
⁵ Theme Heart and Vessels, Division of Valvular and Coronary Disease, Karolinska University Hospital, Stockholm, Sweden.

Abstract

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.

Keywords: AAA, abdominal aortic aneurysm; ALX/FPR2, A lipoxin/formyl peptide receptor 2; ATL, aspirin-triggered lipoxin; Ang II, angiotensin II; LO, lipoxygenase; LX, lipoxin; Rv, resolvin; SPM, specialized pro-resolving mediators; abdominal aortic aneurysms; cardiovascular disease; eicosanoids; inflammation; lipoxygenase.