Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/21706
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dc.contributor.authorQaradakhi, Tawar-
dc.contributor.authorGadanec, Laura K-
dc.contributor.authorTacey, Alexander B-
dc.contributor.authorHare, David L-
dc.contributor.authorBuxton, Brian F-
dc.contributor.authorApostolopoulos, Vasso-
dc.contributor.authorLevinger, Itamar-
dc.contributor.authorZulli, Anthony-
dc.date2019-09-04-
dc.date.accessioned2019-09-09T00:42:27Z-
dc.date.available2019-09-09T00:42:27Z-
dc.date.issued2019-09-04-
dc.identifier.citationCalcified tissue international 2019; online first: 4 September-
dc.identifier.urihttp://ahro.austin.org.au/austinjspui/handle/1/21706-
dc.description.abstractLow circulating levels of undercarboxylated osteocalcin (ucOC) is associated with a higher risk of cardiovascular disease, yet whether ucOC has a direct effect on endothelium-dependent vasorelaxation, or in proximity to its postulated receptor, the class CG protein-coupled receptor (GPCR6A), in blood vessels remains unclear. Immunohistochemistry and proximity ligation assays were used to localize the presence of ucOC and GPRC6A and to determine the physical proximity (< 40 nm) in radial artery segments collected from patients undergoing coronary artery bypass surgery (n = 6) which exhibited calcification (determined by Von Kossa) and aorta from New Zealand white rabbits exhibiting atherosclerotic plaques. Endothelium-dependent vasorelaxation was assessed using cumulative doses of acetylcholine in vitro on abdominal aorta of rabbits fed a normal chow diet (n = 10) and a 4-week atherogenic diet (n = 9) pre-incubated with ucOC (10 ng/mL) or vehicle. Both ucOC and GPRC6A were localized in human and rabbit diseased-blood vessels. Proximity ligation assay staining demonstrated physical proximity of ucOC with GPRC6A only within plaques in rabbit arteries and the endothelium layer of rabbit arterioles. Endothelium-dependent vasorelaxation was impaired in atherogenic abdominal aorta compared to healthy aorta and ucOC attenuated this impairment. ucOC attenuated impaired endothelium-dependent vasorelaxation in rabbit abdominal aorta following an atherogenic diet, however, this effect may be independent of GPRC6A. It is important that future studies determine the underlying cellular mechanisms by which ucOC effects blood vessels as well as whether it can be used as a therapeutic agent against the progression of atherosclerosis.-
dc.language.isoeng-
dc.subjectBlood vessels-
dc.subjectGPRC6A-
dc.subjectOsteocalcin-
dc.subjectPlaque-
dc.subjectRadial artery-
dc.subjectVasorelaxation-
dc.titleThe Effect of Recombinant Undercarboxylated Osteocalcin on Endothelial Dysfunction.-
dc.typeJournal Article-
dc.identifier.journaltitleCalcified tissue international-
dc.identifier.affiliationDepartment of Cardiology, Austin Health, Heidelberg, Victoria, Australiaen
dc.identifier.affiliationInstitute for Health and Sport, Victoria University, Melbourne, VIC, 8001, Australiaen
dc.identifier.affiliationAustralian Institute for Musculoskeletal Science (AIMSS), University of Melbourne and Western Health, St Albans, VIC, 3021, Australiaen
dc.identifier.affiliationThe University of Melbourne, Melbourne, Victoria, Australiaen
dc.identifier.doi10.1007/s00223-019-00600-6-
dc.identifier.orcid0000-0003-2904-5483-
dc.identifier.pubmedid31485687-
Appears in Collections:Journal articles

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