The G-protein coupled receptor ChemR23 determines smooth muscle cell phenotypic switching to enhance high phosphate-induced vascular calcification

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RECERCAT Home > Universitat de Barcelona > IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer > Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer) > View document

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dc.contributor.author	Carracedo, Miguel
dc.contributor.author	Artiach,Gonzalo
dc.contributor.author	Witasp, Anna
dc.contributor.author	Clària i Enrich, Joan
dc.contributor.author	Carlström, Mattias
dc.contributor.author	Laguna Fernández, Andrés
dc.contributor.author	Stenvinkel, Peter
dc.contributor.author	Bäck, Magnus
dc.date	2019-10-25T12:43:58Z
dc.date	2019-12-01T06:10:18Z
dc.date	2019-09-01
dc.date	2019-10-25T12:43:58Z
dc.identifier	0008-6363
dc.identifier	688212
dc.identifier	30597013
dc.identifier.uri	http://hdl.handle.net/2445/143199
dc.description	AIMS: Vascular calcification, a marker of increased cardiovascular risk, is an active process orchestrated by smooth muscle cells. Observational studies indicate that omega-3 fatty acids protect against vascular calcification, but the mechanisms are unknown. The G-protein coupled receptor ChemR23 transduces the resolution of inflammation induced by the omega-3-derived lipid mediator resolvin E1. ChemR23 also contributes to osteoblastic differentiation of stem cells and bone formation, but its role in vascular calcification is unknown. The aim of this study was to establish the role of ChemR23 in smooth muscle cell fate and calcification. METHODS AND RESULTS: Gene expression analysis in epigastric arteries derived from patients with chronic kidney disease and vascular calcification revealed that ChemR23 mRNA levels predicted a synthetic smooth muscle cell phenotype. Genetic deletion of ChemR23 in mice prevented smooth muscle cell de-differentiation. ChemR23-deficient smooth muscle cells maintained a non-synthetic phenotype and exhibited resistance to phosphate-induced calcification. Moreover, ChemR23-deficient mice were protected against vitamin D3-induced vascular calcification. Resolvin E1 inhibited smooth muscle cell calcification through ChemR23. Introduction of the Caenorhabditis elegans Fat1 transgene, leading to an endogenous omega-3 fatty acid synthesis and hence increased substrate for resolvin E1 formation, significantly diminished the differences in phosphate-induced calcification between ChemR23+/+ and ChemR23-/- mice. CONCLUSION: This study identifies ChemR23 as a previously unrecognized determinant of synthetic and osteoblastic smooth muscle cell phenotype, favouring phosphate-induced vascular calcification. This effect may be of particular importance in the absence of ChemR23 ligands, such as resolvin E1, which acts as a calcification inhibitor under hyperphosphatic conditions.
dc.format	22 p.
dc.format	application/pdf
dc.language	eng
dc.publisher	Oxford University Press
dc.relation	Versió postprint del document publicat a: https://doi.org/10.1093/cvr/cvy316
dc.relation	Cardiovascular Research, 2018, vol. 115, num. 10, p. 1557-1566
dc.relation	https://doi.org/10.1093/cvr/cvy316
dc.rights	(c) European Society of Cardiology, 2018
dc.rights	info:eu-repo/semantics/openAccess
dc.subject	Proteïnes de membrana
dc.subject	Múscul llis
dc.subject	Calcificació
dc.subject	Malalties arterials
dc.subject	Membrane proteins
dc.subject	Smooth muscle
dc.subject	Calcification
dc.subject	Arteries Diseases
dc.title	The G-protein coupled receptor ChemR23 determines smooth muscle cell phenotypic switching to enhance high phosphate-induced vascular calcification
dc.type	info:eu-repo/semantics/article
dc.type	info:eu-repo/semantics/acceptedVersion

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