Arterial Expression of the Calcium-Sensing Receptor is Maintained by Physiological Pulsation and Protects Against Calcification.
Calcium-sensing receptor in artery
MetadataShow full item record
Molostvov, G., Hiemstra, T., Fletcher, S., Bland, R., & Zehnder, D. (2015). Arterial Expression of the Calcium-Sensing Receptor is Maintained by Physiological Pulsation and Protects Against Calcification.. PLoS ONE, 10 (e0138833)https://doi.org/10.1371/journal.pone.0138833
Vascular 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.
calcium-sensing receptor, mechanical strain, calcimimetics, calcification, chronic kidney disease
We 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.
External DOI: https://doi.org/10.1371/journal.pone.0138833
This record's URL: https://www.repository.cam.ac.uk/handle/1810/251061
Creative Commons Attribution 4.0
Licence URL: http://creativecommons.org/licenses/by/4.0/