Purpose: The bone derived protein undercarboxylated osteocalcin (ucOC) improves glucose regulation and is associated with a reduced risk of diabetes. In animals, in vivo treatment with ucOC improves vascular function, but this may be due to improved glucose control rather than a direct influence on blood vessels. Moreover, there are conflicting reports on the association of ucOC with cardiovascular outcomes in humans, including reports of adverse effects. The aim of this study was to examine whether ucOC directly influences (positively or negatively) endothelial function in rabbit arteries following incubation in different glucose concentrations.
Methods: Male New Zealand white rabbit arteries were fed a normal or atherogenic diet for 4-weeks. Arteries were incubated ex vivo in 11mM or 20mM glucose solutions for 2-hours and the vasoactivity of ucOC was assessed via several different techniques. Isometric tension analysis was use to assess the vasoactivity of abdominal aortic rings to ucOC pre-incubation (10ng/ml or 30ng/ml). To replicate physiological conditions, perfusion myography techniques were used to assess the vasoactivity of carotid artery segments to ucOC dose response curves (0.3 – 45ng/ml).
Results: In the abdominal aorta, both 10ng/ml and 30ng/ml doses of ucOC did not significantly alter endothelium-dependent (acetylcholine) or endothelium-independent (sodium nitroprusside) blood vessel relaxation in aortic rings following incubation in 11mM or 20mM glucose solutions after either the normal or atherogenic diet (p > 0.05). In the carotid artery, ucOC treatment did not cause any alteration in vasoactivity at any dose of ucOC, compared to a control treatment following either the normal or atherogenic diet (p > 0.05).
Conclusion: ucOC does not have a direct adverse effect on endothelial function in rabbit arteries. The improvement in endothelial function previously reported with ucOC may be a result of improved glucose regulation and not a direct regulatory effect on the vasculature.