ABCC6 deficiency promotes dyslipidemia and atherosclerosis

Abstract ABCC6 deficiency promotes ectopic calcification; however, circumstantial evidence suggested that ABCC6 may also influence atherosclerosis. The present study addressed the role of ABCC6 in atherosclerosis using Ldlr −/− mice and pseudoxanthoma elasticum (PXE) patients. Mice lacking the Abcc6...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Christopher Brampton, Viola Pomozi, Li-Hsieh Chen, Ailea Apana, Sara McCurdy, Janna Zoll, William A. Boisvert, Gilles Lambert, Daniel Henrion, Simon Blanchard, Sheree Kuo, Georges Leftheriotis, Ludovic Martin, Olivier Le Saux
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/095f67c8ae604bf686f99d9c7ce0ab63
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:095f67c8ae604bf686f99d9c7ce0ab63
record_format	dspace
spelling	oai:doaj.org-article:095f67c8ae604bf686f99d9c7ce0ab632021-12-02T14:04:00ZABCC6 deficiency promotes dyslipidemia and atherosclerosis10.1038/s41598-021-82966-y2045-2322https://doaj.org/article/095f67c8ae604bf686f99d9c7ce0ab632021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-82966-yhttps://doaj.org/toc/2045-2322Abstract ABCC6 deficiency promotes ectopic calcification; however, circumstantial evidence suggested that ABCC6 may also influence atherosclerosis. The present study addressed the role of ABCC6 in atherosclerosis using Ldlr −/− mice and pseudoxanthoma elasticum (PXE) patients. Mice lacking the Abcc6 and Ldlr genes were fed an atherogenic diet for 16 weeks before intimal calcification, aortic plaque formation and lipoprotein profile were evaluated. Cholesterol efflux and the expression of several inflammation, atherosclerosis and cholesterol homeostasis-related genes were also determined in murine liver and bone marrow-derived macrophages. Furthermore, we examined plasma lipoproteins, vascular calcification, carotid intima-media thickness and atherosclerosis in a cohort of PXE patients with ABCC6 mutations and compared results to dysmetabolic subjects with increased cardiovascular risk. We found that ABCC6 deficiency causes changes in lipoproteins, with decreased HDL cholesterol in both mice and humans, and induces atherosclerosis. However, we found that the absence of ABCC6 does not influence overall vascular mineralization induced with atherosclerosis. Decreased cholesterol efflux from macrophage cells and other molecular changes such as increased pro-inflammation seen in both humans and mice are likely contributors for the phenotype. However, it is likely that other cellular and/or molecular mechanisms are involved. Our study showed a novel physiological role for ABCC6, influencing plasma lipoproteins and atherosclerosis in a haploinsufficient manner, with significant penetrance.Christopher BramptonViola PomoziLi-Hsieh ChenAilea ApanaSara McCurdyJanna ZollWilliam A. BoisvertGilles LambertDaniel HenrionSimon BlanchardSheree KuoGeorges LeftheriotisLudovic MartinOlivier Le SauxNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-16 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Christopher Brampton Viola Pomozi Li-Hsieh Chen Ailea Apana Sara McCurdy Janna Zoll William A. Boisvert Gilles Lambert Daniel Henrion Simon Blanchard Sheree Kuo Georges Leftheriotis Ludovic Martin Olivier Le Saux ABCC6 deficiency promotes dyslipidemia and atherosclerosis
description	Abstract ABCC6 deficiency promotes ectopic calcification; however, circumstantial evidence suggested that ABCC6 may also influence atherosclerosis. The present study addressed the role of ABCC6 in atherosclerosis using Ldlr −/− mice and pseudoxanthoma elasticum (PXE) patients. Mice lacking the Abcc6 and Ldlr genes were fed an atherogenic diet for 16 weeks before intimal calcification, aortic plaque formation and lipoprotein profile were evaluated. Cholesterol efflux and the expression of several inflammation, atherosclerosis and cholesterol homeostasis-related genes were also determined in murine liver and bone marrow-derived macrophages. Furthermore, we examined plasma lipoproteins, vascular calcification, carotid intima-media thickness and atherosclerosis in a cohort of PXE patients with ABCC6 mutations and compared results to dysmetabolic subjects with increased cardiovascular risk. We found that ABCC6 deficiency causes changes in lipoproteins, with decreased HDL cholesterol in both mice and humans, and induces atherosclerosis. However, we found that the absence of ABCC6 does not influence overall vascular mineralization induced with atherosclerosis. Decreased cholesterol efflux from macrophage cells and other molecular changes such as increased pro-inflammation seen in both humans and mice are likely contributors for the phenotype. However, it is likely that other cellular and/or molecular mechanisms are involved. Our study showed a novel physiological role for ABCC6, influencing plasma lipoproteins and atherosclerosis in a haploinsufficient manner, with significant penetrance.
format	article
author	Christopher Brampton Viola Pomozi Li-Hsieh Chen Ailea Apana Sara McCurdy Janna Zoll William A. Boisvert Gilles Lambert Daniel Henrion Simon Blanchard Sheree Kuo Georges Leftheriotis Ludovic Martin Olivier Le Saux
author_facet	Christopher Brampton Viola Pomozi Li-Hsieh Chen Ailea Apana Sara McCurdy Janna Zoll William A. Boisvert Gilles Lambert Daniel Henrion Simon Blanchard Sheree Kuo Georges Leftheriotis Ludovic Martin Olivier Le Saux
author_sort	Christopher Brampton
title	ABCC6 deficiency promotes dyslipidemia and atherosclerosis
title_short	ABCC6 deficiency promotes dyslipidemia and atherosclerosis
title_full	ABCC6 deficiency promotes dyslipidemia and atherosclerosis
title_fullStr	ABCC6 deficiency promotes dyslipidemia and atherosclerosis
title_full_unstemmed	ABCC6 deficiency promotes dyslipidemia and atherosclerosis
title_sort	abcc6 deficiency promotes dyslipidemia and atherosclerosis
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/095f67c8ae604bf686f99d9c7ce0ab63
work_keys_str_mv	AT christopherbrampton abcc6deficiencypromotesdyslipidemiaandatherosclerosis AT violapomozi abcc6deficiencypromotesdyslipidemiaandatherosclerosis AT lihsiehchen abcc6deficiencypromotesdyslipidemiaandatherosclerosis AT aileaapana abcc6deficiencypromotesdyslipidemiaandatherosclerosis AT saramccurdy abcc6deficiencypromotesdyslipidemiaandatherosclerosis AT jannazoll abcc6deficiencypromotesdyslipidemiaandatherosclerosis AT williamaboisvert abcc6deficiencypromotesdyslipidemiaandatherosclerosis AT gilleslambert abcc6deficiencypromotesdyslipidemiaandatherosclerosis AT danielhenrion abcc6deficiencypromotesdyslipidemiaandatherosclerosis AT simonblanchard abcc6deficiencypromotesdyslipidemiaandatherosclerosis AT shereekuo abcc6deficiencypromotesdyslipidemiaandatherosclerosis AT georgesleftheriotis abcc6deficiencypromotesdyslipidemiaandatherosclerosis AT ludovicmartin abcc6deficiencypromotesdyslipidemiaandatherosclerosis AT olivierlesaux abcc6deficiencypromotesdyslipidemiaandatherosclerosis
_version_	1718392003297804288

ABCC6 deficiency promotes dyslipidemia and atherosclerosis

Ejemplares similares