Transforming growth factor β neutralization finely tunes macrophage phenotype in elastase-induced abdominal aortic aneurysm and is associated with an increase of arginase 1 expression in the aorta.

Journal of Vascular Surgery
Juliette RaffortZiad Mallat

Abstract

Macrophages play a critical role in the initiation and progression of abdominal aortic aneurysm (AAA) and are classically distinguished into M1 "proinflammatory" and M2 "anti-inflammatory" macrophages. Topical application of elastase associated with transforming growth factor β (TGF-β) systemic neutralization reproduces the main pathologic features of human AAA, offering a new model to investigate their role. The aim of this study was to investigate whether macrophages contribute to the expression of canonical M1/M2 markers in the aorta in the AAA model induced by elastase and systemic blockade of TGF-β and whether blocking of TGF-β activity affects macrophage phenotype and the expression of the M2 marker arginase 1 (ARG1). C57Bl/6J male mice (6-8 weeks old) were randomly assigned to three experimental groups: mice that had local application of heat-inactivated elastase or elastase and mice that had elastase application and received injection of anti-TGF-β (elastase + anti-TGF-β group). Monocyte-macrophage depletion was achieved in the elastase + anti-TGF-β group using liposome clodronate. Macrophage phenotype was characterized by quantitative polymerase chain reaction, flow cytometry, and immunohistochemistry. Human infrarenal...Continue Reading

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Citations

Oct 4, 2020·International Journal of Molecular Sciences·Smriti Murali KrishnaJonathan Golledge
Nov 24, 2020·British Journal of Pharmacology·Susana BernalCarmen Gomez-Guerrero
Jul 30, 2021·Clinical and Translational Medicine·Laura Lopez-SanzCarmen Gomez-Guerrero
Jul 28, 2019·Journal of Vascular Surgery·Frank M Davis, Katherine A Gallagher
Aug 31, 2021·Journal of the American Heart Association·Hiroki TanakaRonald L Dalman

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