title: Atherosclerosis differentially affects calcium signalling in endothelial cells from aortic arch and thoracic aorta in Apolipoprotein E knockout mice.
abstract: Apolipoprotein-E knockout (ApoE(-/-)) mice develop hypercholesterolemia and are a useful model of atherosclerosis. Hypercholesterolemia alters intracellular Ca(2+) 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 Ca(2+) 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 Ca(2+) responses were observed in arch endothelial cells. Even with aging and plaque formation, ApoE(-/-) thoracic responses were little changed, however a significantly enhanced Ca(2+) 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 Ca(2+) 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 Ca(2+) 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.
authors.affiliation: Department of Cellular & Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
authors.forename: Clodagh
authors.initials: C
authors.lastname: Prendergast
authors.affiliation: Department of Cellular & Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
authors.forename: John
authors.initials: J
authors.lastname: Quayle
authors.affiliation: Department of Cellular & Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
authors.forename: Theodor
authors.initials: T
authors.lastname: Burdyga
authors.affiliation: Department of Cellular & Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
authors.forename: Susan
authors.initials: S
authors.lastname: Wray
keywords: Apolipoprotein‐E knockout mice; calcium signalling; endothelium; hypercholesterolemia