Abstract
BackgroundThere are conflicting reports on the association of undercarboxylated osteocalcin (ucOC) in cardiovascular disease development, including endothelial function and hypertension. We tested whether ucOC is related to blood pressure and endothelial function in older adults, and if ucOC directly affects endothelial-mediated vasodilation in the carotid artery of rabbits.MethodsIn older adults, ucOC, blood pressure, pulse wave velocity (PWV) and brachial artery flow-mediated dilation (BAFMD) were measured (n = 38, 26 post-menopausal women and 12 men, mean age 73 ± 0.96). The vasoactivity of the carotid artery was assessed in male New Zealand White rabbits following a four-week normal or atherogenic diet using perfusion myography. An ucOC dose response curve (0.3–45 ng/ml) was generated following incubation of the arteries for 2-hours in either normal or high glucose conditions.ResultsucOC levels were higher in normotensive older adults compared to those with stage 2 hypertension (p < 0.05), particularly in women (p < 0.01). In all participants, higher ucOC was associated with lower PWV (p < 0.05), but not BAFMD (p > 0.05). In rabbits, ucOC at any dose did not alter vasoactivity of the carotid artery, either following a normal or an atherogenic diet (p > 0.05).ConclusionIncreased ucOC is associated with lower blood pressure and increased arterial stiffness, particularly in post-menopausal women. However, ucOC administration has no direct short-term effect on endothelial function in rabbit arteries. Future studies should explore whether treatment with ucOC, in vivo, has direct or indirect effects on blood vessel function.
Highlights
The bone derived hormone osteocalcin (OC) is a vitamin K-dependent protein that exists in several biological forms
Higher undercarboxylated osteocalcin (ucOC) was associated with lower pulse wave velocity (PWV) (p < 0.05), but not brachial artery flowmediated dilation (BAFMD) (p > 0.05)
Increased ucOC is associated with lower blood pressure and increased arterial stiffness, in post-menopausal women
Summary
The bone derived hormone osteocalcin (OC) is a vitamin K-dependent protein that exists in several biological forms. Not all studies are in agreement [9, 10] Given these findings, it is of interest to investigate whether ucOC is involved in other biological functions within the body [11, 12]. As metabolic and cardiovascular diseases (CVD) share common pathological links [13], it is of particular interest to examine the interaction of ucOC with endothelial function and atherosclerosis progression. This is important, in the context of CVD, and because ucOC could be targeted as a future therapy for metabolic diseases. There are conflicting reports on the association of undercarboxylated osteocalcin (ucOC) in cardiovascular disease development, including endothelial function and hypertension. We tested whether ucOC is related to blood pressure and endothelial function in older adults, and if ucOC directly affects endothelial-mediated vasodilation in the carotid artery of rabbits.
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