The Downstream Regulation of Chemokine Receptor Signalling: Implications for Atherosclerosis

Table 1

GPCR signalling regulatory proteins in atherosclerosis.

Regulatory protein	Experimental evidence in atherosclerosis	Reference
β-arrestin 2	(i) β-arrestin 2 ^−/−Ldlr ^−/− mice have reduced aortic atherosclerosis; (ii) β-arrestin 2 ^−/−Ldlr ^−/− mice have reduced SMC content in the aortic root	[69]
GRK2	(i) GRK2 ^+/−Ldlr ^−/− chimeric mice have reduced atherosclerosis and necrotic core in the aortic root; (ii) GRK2 ^+/−Ldlr ^−/− chimeric mice have increased macrophage and VSMC content in aortic root lesions; (iii) CCL5-induced in vivo migration of leukocytes is increased GRK2 ^+/−Ldlr ^−/− chimeras	[72]
GRK5	(i) GRK5 ^−/−ApoE ^−/− mice have increased atherosclerosis in aorta than ApoE ^−/− mice; (ii) GRK5 ^−/−ApoE ^−/− mice have increased macrophage and VSMC proliferation in aortic root lesions; (iii) GRK5 ^−/− monocytes have increased migration to atherogenic stimuli in vitro	[73]
RGS1	(i) Rgs1 expression is upregulated in thoracic aortas from 𝐴𝑝𝑜𝐸^−/− mice at 16 weeks of age in comparison to 𝐴𝑝𝑜𝐸^−/− mice at 8 weeks of age and wild-type C57BL/6J mice; (ii) Rgs1 was found to be upregulated in unstable segments of plaque from human carotid endarterectomy specimens over stable segments from the same patient; (iii) Rgs1 upregulated in human atherosclerotic coronary arteries	Unpublished data, Channon laboratory [74]; [68]
RGS2	(i) Genetic polymorphisms in Rgs2 have been associated with intima-media thickening of the carotid artery in patients with hypertension	[75]
RGS5	(i) Rgs5 expression is downregulated in SMCs of atherosclerotic plaques from nonhuman primates	[76]