The Effect of Recombinant Undercarboxylated Osteocalcin on Endothelial Dysfunction

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 a rterioles. 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 ...
Source: Calcified Tissue International - Category: Orthopaedics Source Type: research