title: Arterial Expression of the Calcium-Sensing Receptor Is Maintained by Physiological Pulsation and Protects against Calcification.
abstract: 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.
  
  
  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.
authors.affiliation: The Clinical Sciences Research Laboratory, Warwick Medical School, University of Warwick, Coventry, United Kingdom.
authors.forename: Guerman
authors.initials: G
authors.lastname: Molostvov
authors.affiliation: School of Clinical Medicine, University of Cambridge, Cambridge, United Kingdom; Cambridge Clinical Trials Unit, Addenbrooke's Hospital, Cambridge, United Kingdom.
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Hiemstra
authors.affiliation: Department of Nephrology, University Hospital Coventry and Warwickshire, Coventry, United Kingdom.
authors.forename: Simon
authors.initials: S
authors.lastname: Fletcher
authors.affiliation: The Clinical Sciences Research Laboratory, Warwick Medical School, University of Warwick, Coventry, United Kingdom.
authors.forename: Rosemary
authors.initials: R
authors.lastname: Bland
authors.affiliation: The Clinical Sciences Research Laboratory, Warwick Medical School, University of Warwick, Coventry, United Kingdom; Department of Nephrology, University Hospital Coventry and Warwickshire, Coventry, United Kingdom.
authors.forename: Daniel
authors.initials: D
authors.lastname: Zehnder
mesh_terms: D000328:Adult; D000368:Aged; D001011:Aorta / Q000166:cytology / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology*; D002478:Cells, Cultured; D020219:Chondrogenesis / Q000187:drug effects; D050659:Core Binding Factor Alpha 1 Subunit / Q000096:biosynthesis / Q000235:genetics; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism*; D010006:Osteoblasts / Q000166:cytology; D010012:Osteogenesis / Q000187:drug effects; D010627:Phenethylamines / Q000494:pharmacology; D010750:Phosphoproteins / Q000096:biosynthesis / Q000235:genetics; D011437:Propylamines / Q000494:pharmacology; D011673:Pulsatile Flow / Q000502:physiology*; D044169:Receptors, Calcium-Sensing / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D013314:Stress, Mechanical; D014162:Transfection; D061205:Vascular Calcification / Q000503:physiopathology / Q000517:prevention & control*; D055815:Young Adult
chemical_list: C095550:CASR protein, human; D050659:Core Binding Factor Alpha 1 Subunit; C513309:DMP1 protein, human; D016326:Extracellular Matrix Proteins; C107873:N-(2-chlorophenylpropyl)-1-(3-methoxyphenyl)ethylamine; D010627:Phenethylamines; D010750:Phosphoproteins; D011437:Propylamines; C493709:RUNX2 protein, human; D044169:Receptors, Calcium-Sensing; D011993:Recombinant Fusion Proteins; D002118:Calcium