The Effect of Recombinant Undercarboxylated Osteocalcin on Endothelial Dysfunction

Area of Science:

• Cardiovascular Research
• Endocrinology
• Vascular Biology

Background:

• Low circulating undercarboxylated osteocalcin (ucOC) correlates with increased cardiovascular disease risk.
• The direct impact of ucOC on vascular endothelium-dependent vasorelaxation and its interaction with the G protein-coupled receptor 6A (GPRC6A) in blood vessels remain largely uncharacterized.

Purpose of the Study:

• To investigate the localization of ucOC and GPRC6A in diseased human and rabbit blood vessels.
• To assess the effect of ucOC on endothelium-dependent vasorelaxation in an experimental atherosclerosis model.
• To determine if ucOC's vascular effects are mediated through GPRC6A.

Main Methods:

• Immunohistochemistry and proximity ligation assays were used to localize ucOC and GPRC6A in human radial arteries and rabbit aortas.
• Endothelium-dependent vasorelaxation was measured in rabbit aortas using acetylcholine, with or without ucOC treatment, after normal or atherogenic diet induction.
• Vessel calcification was assessed using Von Kossa staining.

Main Results:

• Both ucOC and GPRC6A were detected in diseased human and rabbit blood vessels.
• Physical proximity between ucOC and GPRC6A was observed within atherosclerotic plaques and the endothelium of rabbit arterioles.
• ucOC treatment attenuated the impaired endothelium-dependent vasorelaxation in rabbits fed an atherogenic diet, suggesting a protective vascular role potentially independent of GPRC6A.

Conclusions:

• ucOC is present in diseased vasculature and can improve endothelial function in an atherosclerosis model.
• The beneficial effects of ucOC on vasorelaxation in this model may not be directly mediated by GPRC6A.
• Further research is warranted to elucidate the mechanisms of ucOC's action on blood vessels and its therapeutic potential for atherosclerosis.