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: Jyoti Patel, Eileen McNeill, Gillian Douglas, Ashley B Hale, Joseph de Bono, Regent Lee, Asif J Iqbal, Daniel Regan-Komito, Elena Stylianou, David R Greaves, Keith M Channon
• Journal: Nature communications (Nat Commun) Vol. 6 Pg. 6614 (Mar 18 2015) ISSN: 2041-1723 [Electronic] England
• PMID: 25782711 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Chemokines
• RGS Proteins
• RGS1 protein, human
• Receptors, Chemokine
• Rgs1 protein, mouse

Topics

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