Atherosclerosis differentially affects calcium signalling in endothelial cells from aortic arch and thoracic aorta in Apolipoprotein E knockout mice

Prendergast, Clodagh ORCID: 0000-0002-7678-7693, Quayle, John ORCID: 0000-0003-2762-5011, Burdyga, Theodor and Wray, Susan ORCID: 0000-0002-0086-1359 (2014) Atherosclerosis differentially affects calcium signalling in endothelial cells from aortic arch and thoracic aorta in Apolipoprotein E knockout mice. Physiological Reports, 2 (10). e12171-.

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Abstract

Apolipoprotein-E knockout (ApoE-/-) mice develop hypercholesterolemia and are a useful model of atherosclerosis. Hypercholesterolemia alters intracellular Ca2+ signalling in vascular endothelial cells but our understanding of these changes, especially in the early stages of the disease process, is limited. We therefore determined whether carbachol-mediated endothelial Ca2+ signals differ in plaque-prone aortic arch compared to plaque-resistant thoracic aorta, of wild-type and ApoE-/- mice, and how this is affected by age and the presence of hypercholesterolemia. The extent of plaque development was determined using en-face staining with Sudan IV. Tissues were obtained from wild-type and ApoE-/- mice at 10 weeks (pre-plaques) and 24 weeks (established plaques). We found that even before development of plaques, significantly increased Ca2+ responses were observed in arch endothelial cells. Even with aging and plaque formation, ApoE-/- thoracic responses were little changed, however a significantly enhanced Ca2+ response was observed in arch, both adjacent to and away from lesions. In wild-type mice of any age, 1-2% of cells had oscillatory Ca2+ responses. In young ApoE-/- and plaque-free regions of older ApoE-/-, this is unchanged. However a significant increase in oscillations (~13-15%) occurred in thoracic and arch cells adjacent to lesions in older mice. Our data suggest that Ca2+ signals in endothelial cells show specific changes both before and with plaque formation, that these changes are greatest in plaque-prone aortic arch cells, and that these changes will contribute to the reported deterioration of endothelium in atherosclerosis.

Item Type:	Article
Uncontrolled Keywords:	Apolipoprotein‐E knockout mice, calcium signalling, endothelium, hypercholesterolemia
Depositing User:	Symplectic Admin
Date Deposited:	17 Nov 2014 15:37
Last Modified:	17 Dec 2022 01:33
DOI:	10.14814/phy2.12171
Publisher's Statement :	© 2014 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/2001480