title: RGS1 regulates myeloid cell accumulation in atherosclerosis and aortic aneurysm rupture through altered chemokine signalling.
abstract: 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.
authors.affiliation: 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.
authors.forename: Jyoti
authors.initials: J
authors.lastname: Patel
authors.affiliation: 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.
authors.forename: Eileen
authors.initials: E
authors.lastname: McNeill
authors.affiliation: 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.
authors.forename: Gillian
authors.initials: G
authors.lastname: Douglas
authors.affiliation: 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.
authors.forename: Ashley B
authors.initials: AB
authors.lastname: Hale
authors.affiliation: 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.
authors.forename: Joseph
authors.initials: J
authors.lastname: de Bono
authors.affiliation: 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.
authors.forename: Regent
authors.initials: R
authors.lastname: Lee
authors.affiliation: Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, UK.
authors.forename: Asif J
authors.initials: AJ
authors.lastname: Iqbal
authors.affiliation: Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, UK.
authors.forename: Daniel
authors.initials: D
authors.lastname: Regan-Komito
authors.affiliation: Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK.
authors.forename: Elena
authors.initials: E
authors.lastname: Stylianou
authors.affiliation: Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, UK.
authors.forename: David R
authors.initials: DR
authors.lastname: Greaves
authors.affiliation: 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.
authors.forename: Keith M
authors.initials: KM
authors.lastname: Channon
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism; D001014:Aortic Aneurysm / Q000235:genetics / Q000378:metabolism*; D050197:Atherosclerosis / Q000378:metabolism*; D001794:Blood Pressure; D016026:Bone Marrow Transplantation; D018925:Chemokines / Q000378:metabolism*; D002633:Chemotaxis; D005434:Flow Cytometry; D006801:Humans; D007249:Inflammation; D007962:Leukocytes / Q000166:cytology / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009000:Monocytes / Q000166:cytology; D020710:RGS Proteins / Q000378:metabolism*; D019707:Receptors, Chemokine / Q000378:metabolism; D015398:Signal Transduction; D014652:Vascular Diseases / Q000378:metabolism
chemical_list: D018925:Chemokines; D020710:RGS Proteins; C080831:RGS1 protein, human; D019707:Receptors, Chemokine; C488188:Rgs1 protein, mouse