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dc.contributor.authorMolostvov, Guermanen
dc.contributor.authorHiemstra, Thomasen
dc.contributor.authorFletcher, Simonen
dc.contributor.authorBland, Rosemaryen
dc.contributor.authorZehnder, Danielen
dc.date.accessioned2015-09-18T12:04:48Z
dc.date.available2015-09-18T12:04:48Z
dc.date.issued2015-10-05en
dc.identifier.citationPLoS ONE 2015, 10(10): e0138833. doi:10.1371/journal.pone.0138833en
dc.identifier.issn1932-6203
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/251061
dc.description.abstractVascular calcification (VC) is common in chronic kidney disease (CKD) and contributes to cardiovascular mortality. The calcium-sensing receptor (CaSR) is present in human artery, senses extracellular calcium and may directly modulate VC. Objective: to investigate the association between arterial cyclic strain, CaSR expression and VC. Methods and Results: human aortic smooth muscle cells (HAoSMC) were cultured under static or strained conditions, with exposure to CaSR agonists, the calcimimetic R568, and after CaSR silencing and over-expression. High extracellular calcium reduced CaSR expression and promoted osteochondrogenic transformation and calcium deposition. This was partially prevented by cyclic strain and exposure to R568. CaSR silencing enhanced calcification and osteochondrogenic transformation, whereas CaSR over-expression attenuated this procalcific response, demonstrating a central role for the CaSR in the response to cyclic strain and regulation of VC. In arterial explants from CKD patients (n=11) and controls (n=9), exposure to R568 did not significantly alter calcium deposition, osteochondrogenic markers or total artery calcium content. Conclusions: physiological mechanical strain is important for arterial homeostasis and may protect arteries from VC. The beneficial effects of cyclic strain may be mediated via the CaSR.
dc.description.sponsorshipWe are grateful to Professor A.R. Bradwell (Binding Site) for generating CaSR antibody and MRC Infrastructure Award (G4500017) 'Bioinformatics and Structural Biology in Life Sciences' for CaSR peptide design. R-568 and S-568 was a kind gift from Amgen USA.
dc.languageEnglishen
dc.language.isoenen
dc.publisherPLoS
dc.rightsCreative Commons Attribution 4.0
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectcalcium-sensing receptoren
dc.subjectmechanical strainen
dc.subjectcalcimimeticsen
dc.subjectcalcificationen
dc.subjectchronic kidney diseaseen
dc.titleArterial Expression of the Calcium-Sensing Receptor is Maintained by Physiological Pulsation and Protects Against Calcification.en
dc.title.alternativeCalcium-sensing receptor in arteryen
dc.typeArticle
dc.description.versionThis is the final version of the article. It first appeared from PLOS via http://dx.doi.org/10.1371/journal.pone.0138833en
prism.numbere0138833en
prism.publicationDate2015en
prism.publicationNamePLoS ONEen
prism.volume10en
dc.rioxxterms.funderMRC
dcterms.dateAccepted2015-09-03en
rioxxterms.versionofrecord10.1371/journal.pone.0138833en
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2015-10-05en
dc.contributor.orcidHiemstra, Thomas [0000-0002-2115-8689]
dc.identifier.eissn1932-6203
rioxxterms.typeJournal Article/Reviewen


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Creative Commons Attribution 4.0
Except where otherwise noted, this item's licence is described as Creative Commons Attribution 4.0