Altered gene expression in early atherosclerosis is blocked by low level apolipoprotein E.

<h4>Background</h4>Mice deficient in apolipoprotein E (apoE(-/-)) develop atherosclerosis. The possible linkage between expression of adhesion molecules/cofactors and atherosclerosis was probed at the level of mRNA and protein expression. The hypothesis of a linkage between changes of ad...

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Autores principales:	Yanqing Ma, Craig C Malbon, David L Williams, Fayanne E Thorngate
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2008
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/310ba749fe6b44a083bf4870d55fa14c
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spelling	oai:doaj.org-article:310ba749fe6b44a083bf4870d55fa14c2021-11-25T06:12:00ZAltered gene expression in early atherosclerosis is blocked by low level apolipoprotein E.1932-620310.1371/journal.pone.0002503https://doaj.org/article/310ba749fe6b44a083bf4870d55fa14c2008-06-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/18560564/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Mice deficient in apolipoprotein E (apoE(-/-)) develop atherosclerosis. The possible linkage between expression of adhesion molecules/cofactors and atherosclerosis was probed at the level of mRNA and protein expression. The hypothesis of a linkage between changes of adhesion molecules/cofactors and atherosclerosis was tested further by suppression of aortic lesion formation in apoE(-/-) mice by expression of very low levels of transgenic apolipoprotein E.<h4>Methodology/principal findings</h4>We show that at 8.5 months of age, the apoE(-/-) mice display elevated expression of mRNA for LFA-1, MAC-1, VCAM-1, ICAM-1, and for CD44, as well as MCP-1, cathepsin B, and COX-2 (but not that for eNOS) in atherosclerotic aortic arches. At earlier age, (10-13 week old) apoE(-/-) mice already display elevated expression of mRNA of CD44, LFA-1, MAC-1, VCAM-1, ICAM-1, cathepsin, and of COX-2 in lesioned aortic arches. Expressing very low levels of transgenic apolipoprotein E suppresses both aortic lesions and the expression of mRNA of LFA-1, VCAM-1, MCP-1, cathepsin B, and of ICAM-1 in ApoE(-/-) mice. We tested at the level of protein, the observations obtained for mRNA expression. CD11a (a component of LFA-1), VCAM-1 and cathepsin B expression was found to be elevated in apoE(-/-) aortas at 8-9 months; low level expression of transgenic apolipoprotein E rectifies these changes.<h4>Conclusions/significance</h4>Atherosclerotic lesions in apoE(-/-) mice are detected as early as 4 weeks of age. Expression of low levels of apoE is shown to be both atheroprotective and to suppress these changes in key adhesion and inflammatory molecules observed in early atherosclerotic lesions.Yanqing MaCraig C MalbonDavid L WilliamsFayanne E ThorngatePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 3, Iss 6, p e2503 (2008)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yanqing Ma Craig C Malbon David L Williams Fayanne E Thorngate Altered gene expression in early atherosclerosis is blocked by low level apolipoprotein E.
description	<h4>Background</h4>Mice deficient in apolipoprotein E (apoE(-/-)) develop atherosclerosis. The possible linkage between expression of adhesion molecules/cofactors and atherosclerosis was probed at the level of mRNA and protein expression. The hypothesis of a linkage between changes of adhesion molecules/cofactors and atherosclerosis was tested further by suppression of aortic lesion formation in apoE(-/-) mice by expression of very low levels of transgenic apolipoprotein E.<h4>Methodology/principal findings</h4>We show that at 8.5 months of age, the apoE(-/-) mice display elevated expression of mRNA for LFA-1, MAC-1, VCAM-1, ICAM-1, and for CD44, as well as MCP-1, cathepsin B, and COX-2 (but not that for eNOS) in atherosclerotic aortic arches. At earlier age, (10-13 week old) apoE(-/-) mice already display elevated expression of mRNA of CD44, LFA-1, MAC-1, VCAM-1, ICAM-1, cathepsin, and of COX-2 in lesioned aortic arches. Expressing very low levels of transgenic apolipoprotein E suppresses both aortic lesions and the expression of mRNA of LFA-1, VCAM-1, MCP-1, cathepsin B, and of ICAM-1 in ApoE(-/-) mice. We tested at the level of protein, the observations obtained for mRNA expression. CD11a (a component of LFA-1), VCAM-1 and cathepsin B expression was found to be elevated in apoE(-/-) aortas at 8-9 months; low level expression of transgenic apolipoprotein E rectifies these changes.<h4>Conclusions/significance</h4>Atherosclerotic lesions in apoE(-/-) mice are detected as early as 4 weeks of age. Expression of low levels of apoE is shown to be both atheroprotective and to suppress these changes in key adhesion and inflammatory molecules observed in early atherosclerotic lesions.
format	article
author	Yanqing Ma Craig C Malbon David L Williams Fayanne E Thorngate
author_facet	Yanqing Ma Craig C Malbon David L Williams Fayanne E Thorngate
author_sort	Yanqing Ma
title	Altered gene expression in early atherosclerosis is blocked by low level apolipoprotein E.
title_short	Altered gene expression in early atherosclerosis is blocked by low level apolipoprotein E.
title_full	Altered gene expression in early atherosclerosis is blocked by low level apolipoprotein E.
title_fullStr	Altered gene expression in early atherosclerosis is blocked by low level apolipoprotein E.
title_full_unstemmed	Altered gene expression in early atherosclerosis is blocked by low level apolipoprotein E.
title_sort	altered gene expression in early atherosclerosis is blocked by low level apolipoprotein e.
publisher	Public Library of Science (PLoS)
publishDate	2008
url	https://doaj.org/article/310ba749fe6b44a083bf4870d55fa14c
work_keys_str_mv	AT yanqingma alteredgeneexpressioninearlyatherosclerosisisblockedbylowlevelapolipoproteine AT craigcmalbon alteredgeneexpressioninearlyatherosclerosisisblockedbylowlevelapolipoproteine AT davidlwilliams alteredgeneexpressioninearlyatherosclerosisisblockedbylowlevelapolipoproteine AT fayanneethorngate alteredgeneexpressioninearlyatherosclerosisisblockedbylowlevelapolipoproteine
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Altered gene expression in early atherosclerosis is blocked by low level apolipoprotein E.

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