Regulator of G-protein signalling 5 protects against atherosclerosis in apolipoprotein E-deficient mice.

Abstract

BACKGROUND AND PURPOSE:

Atherosclerosis is a chronic inflammatory disease, in which 'vulnerable plaques' have been recognized as the underlying risk factor for coronary disease. Regulator of G-protein signalling (RGS) 5 controls endothelial cell function and inflammation. In this study, we explored the effect of RGS5 on atherosclerosis and the potential underlying mechanisms.

EXPERIMENTAL APPROACH:

RGS5(-/-) apolipoprotein E (ApoE)(-/-) and ApoE(-/-) littermates were fed a high-fat diet for 28 weeks. Total aorta surface and lipid accumulation were measured by Oil Red O staining and haematoxylin-eosin staining was used to analyse the morphology of atherosclerotic lesions. Inflammatory cell infiltration and general inflammatory mediators were examined by immunofluorescence staining. Apoptotic endothelial cells and macrophages were assayed with TUNEL. Expression of RGS5 and adhesion molecules, and ERK1/2 phosphorylation were evaluated by co-staining with CD31. Expression of mRNA and protein were determined by quantitative real-time PCR and Western blotting respectively.

KEY RESULTS:

Atherosclerotic phenotypes were significantly accelerated in RGS5(-/-) ApoE(-/-) mice, as indicated by increased inflammatory mediator expression and apoptosis of endothelial cells and macrophages. RGS5 deficiency enhanced instability of vulnerable plaques by increasing infiltration of macrophages in parallel with the accumulation of lipids, and decreased smooth muscle cell and collagen content. Mechanistically, increased activation of NF-κB and MAPK/ERK 1/2 could be responsible for the accelerated development of atherosclerosis in RGS5-deficient mice.

CONCLUSIONS AND IMPLICATIONS:

RGS5 deletion accelerated development of atherosclerosis and decreased the stability of atherosclerotic plaques partly through activating NF-κB and the MEK-ERK1/2 signalling pathways.

• Authors: Wen-Lin Cheng, Pi-Xiao Wang, Tao Wang, Yan Zhang, Cheng Du, Hongliang Li, Yong Ji
• Journal: British journal of pharmacology (Br J Pharmacol) Vol. 172 Issue 23 Pg. 5676-89 (Dec 2015) ISSN: 1476-5381 [Electronic] England
• PMID: 25363362 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 The British Pharmacological Society.

Chemical References

• Apolipoproteins E
• RGS Proteins
• Rgs5 protein, mouse

Topics

• Animals
• Apolipoproteins E (deficiency)
• Atherosclerosis (metabolism, prevention & control)
• Mice
• Mice, Knockout
• RGS Proteins (deficiency, genetics, metabolism)