RGS1 regulates myeloid cell accumulation in atherosclerosis and aortic aneurysm rupture through altered chemokine signalling

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 s...

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Príomhchruthaitheoirí: Patel, J, McNeill, E, Douglas, G, Hale, A, de Bono, J, Lee, R, Iqbal, A, Regan-Komito, D, Stylianou, E, Greaves, D, Channon, K
Formáid: Journal article
Teanga:English
Foilsithe / Cruthaithe: Nature Publishing Group 2015
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author Patel, J
McNeill, E
Douglas, G
Hale, A
de Bono, J
Lee, R
Iqbal, A
Regan-Komito, D
Stylianou, E
Greaves, D
Channon, K
author_facet Patel, J
McNeill, E
Douglas, G
Hale, A
de Bono, J
Lee, R
Iqbal, A
Regan-Komito, D
Stylianou, E
Greaves, D
Channon, K
author_sort Patel, J
collection OXFORD
description 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.
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spelling oxford-uuid:976c8bfe-97d8-45e8-b024-b659a28b4b022022-03-26T23:59:36ZRGS1 regulates myeloid cell accumulation in atherosclerosis and aortic aneurysm rupture through altered chemokine signallingJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:976c8bfe-97d8-45e8-b024-b659a28b4b02EnglishSymplectic Elements at OxfordNature Publishing Group2015Patel, JMcNeill, EDouglas, GHale, Ade Bono, JLee, RIqbal, ARegan-Komito, DStylianou, EGreaves, DChannon, KChemokine 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.
spellingShingle Patel, J
McNeill, E
Douglas, G
Hale, A
de Bono, J
Lee, R
Iqbal, A
Regan-Komito, D
Stylianou, E
Greaves, D
Channon, K
RGS1 regulates myeloid cell accumulation in atherosclerosis and aortic aneurysm rupture through altered chemokine signalling
title RGS1 regulates myeloid cell accumulation in atherosclerosis and aortic aneurysm rupture through altered chemokine signalling
title_full RGS1 regulates myeloid cell accumulation in atherosclerosis and aortic aneurysm rupture through altered chemokine signalling
title_fullStr RGS1 regulates myeloid cell accumulation in atherosclerosis and aortic aneurysm rupture through altered chemokine signalling
title_full_unstemmed RGS1 regulates myeloid cell accumulation in atherosclerosis and aortic aneurysm rupture through altered chemokine signalling
title_short RGS1 regulates myeloid cell accumulation in atherosclerosis and aortic aneurysm rupture through altered chemokine signalling
title_sort rgs1 regulates myeloid cell accumulation in atherosclerosis and aortic aneurysm rupture through altered chemokine signalling
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