Background: The bone derived protein undercarboxylated osteocalcin (ucOC) is implicated as a therapeutic target in glycaemic control and energy metabolism. Growing research suggests an association between ucOC and cardiovascular disease outcomes such as blood vessel function. However, due to conflicting reports it is unknown if this effect is positive or negative and whether any effect occurs directly in the vasculature, or indirectly via its metabolic influences.
Methods: Rabbits (n = 6 - 9) were fed a normal chow diet or the same diet combined with 1% methionine, 0.5% cholesterol and 5% peanut oil (atherogenic diet) for 4 weeks. The abdominal aorta was dissected and incubated ex-vivo for two hours in control or high glucose (20mM) media. Isometric tension myography was used to study the vasodilatory response of aortic rings to treatment of recombinant ucOC (control, 10ng/ml or 30ng/ml), 5 minutes prior to completing dose response curves (-9M to -5M) to acetylcholine or sodium nitroprusside to assess endothelium dependent and endothelium independent vasodilation, respectively.
Results: The atherogenic diet caused an increase in blood glucose by 25% (p<0.01), without altering insulin concentration, indicating insulin resistance. In the normal diet fed group, ucOC (10ng/ml) cause a significant shift of the dose response curve to the left at a single dose, improving relaxation by 15% (p<0.05) for the control and 20% (p<0.01) for the 20mM incubation. However, ucOC did not effect the maximal relaxation of the aorta to acetylcholine. UcOC caused no change in relaxation in the sodium nitroprusside dose response curves, indicating ucOC functions via the endothelium.
Conclusion: UcOC may potentially enhance relaxation in healthy and hyperglycaemic conditions via endothelium dependent mechanisms, yet further investigation is required. Importantly, ucOC was found to have no harmful impact on blood vessel function and therefore may be investigated as a therapeutic option for metabolic diseases.