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Chemokine signalling drives monocyte recruitment in atherosclerosis and aortic aneurysms. The mechanisms that lead to retention and accumulation of macrophages in the vascular wall remain unclear. Regulator of G-Protein Signalling-1 (RGS1) deactivates G-protein signalling, reducing the response to sustained chemokine stimulation. Here we show that Rgs1 is upregulated in atherosclerotic plaque and aortic aneurysms. Rgs1 reduces macrophage chemotaxis and desensitizes chemokine receptor signalling. In early atherosclerotic lesions, Rgs1 regulates macrophage accumulation and is required for the formation and rupture of Angiotensin II-induced aortic aneurysms, through effects on leukocyte retention. Collectively, these data reveal a role for Rgs1 in leukocyte trafficking and vascular inflammation and identify Rgs1, and inhibition of chemokine receptor signalling as potential therapeutic targets in vascular disease.

Original publication

DOI

10.1038/ncomms7614

Type

Journal article

Journal

Nature Communications

Publication Date

18/03/2015

Volume

6

Addresses

1] Division of Cardiovascular Medicine, British Heart Foundation Centre of Research Excellence, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, UK [2] Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.

Keywords

Aorta, Leukocytes, Monocytes, Macrophages, Animals, Mice, Knockout, Humans, Mice, Vascular Diseases, Aortic Aneurysm, Inflammation, RGS Proteins, Receptors, Chemokine, Chemokines, Bone Marrow Transplantation, Flow Cytometry, Signal Transduction, Chemotaxis, Blood Pressure, Male, Atherosclerosis