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Millar, Sophie (2020) Osteocalcin and the vasculature. PhD thesis, University of Nottingham.

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Abstract

Osteocalcin (OCN) is an intriguing hormone having established roles throughout the body beyond its origin of the bone extra cellular matrix. Uncarboxylated osteocalcin (ucOCN) is the major form found within the circulation. However, knowledge surrounding the effects of ucOCN within the vasculature is very limited. Therefore, the aim of this thesis was to create a novel portfolio of work examining the effects of ucOCN within the vasculature.

A systematic review was performed to examine the relationship between osteocalcin and atherosclerosis or vascular calcification. In vitro experiments were conducted to establish a broad range of biological responses of human aortic endothelial cells (HAECs) and smooth muscle cells (HASMCs) to ucOCN. These included intracellular signalling, protein secretion, migration, proliferation, angiogenesis, and permeability investigations. We further examined whether ucOCN affected inflammation in HAECs and HASMCs, and vascular calcification in HASMCs.

From the literature, no definitive association was determined between OCN and vascular calcification or atherosclerosis. In in vitro investigations, we found ucOCN has direct biological activity in vascular cells and increases proliferation. Cell permeability, migration and angiogenesis were not affected by ucOCN. ucOCN did not affect inflammation in either cell type and is unlikely to have importance in the process of atherosclerosis. In calcification experiments, ucOCN did not increase or speed up the extent of calcification, nor did it have any inhibitory effects. Thus, ucOCN is unlikely to have a contributing role to the progression of vascular calcification.

In conclusion, ucOCN does not appear to have a direct physiologically relevant role in the vasculature. It may be relevant to assess the effects of osteocalcin on cardiovascular health and disease at a whole body level, and to explore effects in the context of diabetes.

Item Type:	Thesis (University of Nottingham only) (PhD)
Supervisors:	O'Sullivan, Saoirse Anderson, Susan
Keywords:	Osteocalcin; Vasculature; Atherosclerosis; Human aortic endothelial cells; Smooth muscle cells; Inflammation
Subjects:	W Medicine and related subjects (NLM Classification) > WG Cardiocascular system
Faculties/Schools:	UK Campuses > Faculty of Medicine and Health Sciences > School of Medicine
Item ID:	59964
Depositing User:	Millar, Sophie
Date Deposited:	06 Oct 2023 12:26
Last Modified:	06 Oct 2023 12:26
URI:	https://eprints.nottingham.ac.uk/id/eprint/59964

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