Hematopoietic upstream stimulating factor 1 deficiency is associated with increased atherosclerosis susceptibility in LDL receptor knockout mice

Abstract Total body upstream stimulatory factor 1 (USF1) deficiency in mice is associated with brown adipose tissue activation and a marked protection against the development of obesity and atherosclerotic lesions. Functional expression of USF1 has also been detected in monocytes and monocyte-derive...

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Autores principales:	Menno Hoekstra, Baoyan Ren, Pirkka-Pekka Laurila, Reeni B. Hildebrand, Jarkko Soronen, Vanessa Frodermann, Zhuang Li, Mariëtte R. Boon, Janine J. Geerling, Patrick C. N. Rensen, Matti Jauhiainen, Miranda Van Eck
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/17a14d3adad549cc9cc447dc81e3bc71
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spelling	oai:doaj.org-article:17a14d3adad549cc9cc447dc81e3bc712021-12-02T16:27:50ZHematopoietic upstream stimulating factor 1 deficiency is associated with increased atherosclerosis susceptibility in LDL receptor knockout mice10.1038/s41598-021-95858-y2045-2322https://doaj.org/article/17a14d3adad549cc9cc447dc81e3bc712021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-95858-yhttps://doaj.org/toc/2045-2322Abstract Total body upstream stimulatory factor 1 (USF1) deficiency in mice is associated with brown adipose tissue activation and a marked protection against the development of obesity and atherosclerotic lesions. Functional expression of USF1 has also been detected in monocytes and monocyte-derived macrophages. In the current study we therefore tested whether selective hematopoietic USF1 deficiency can also beneficially impact the development of atherosclerosis. For this purpose, LDL receptor knockout mice were transplanted with bone marrow from USF1 knockout mice or their wild-type littermate controls and subsequently fed a Western-type diet for 20 weeks to stimulate atherosclerotic lesion development. Strikingly, absence of USF1 function in bone marrow-derived cells was associated with exacerbated blood leukocyte (+ 100%; P < 0.01) and peritoneal leukocyte (+ 50%; P < 0.05) lipid loading and an increased atherosclerosis susceptibility (+ 31%; P < 0.05). These effects could be attributed to aggravated hyperlipidemia, i.e. higher plasma free cholesterol (+ 33%; P < 0.001) and cholesteryl esters (+ 39%; P < 0.001), and the development of hepatosteatosis. In conclusion, we have shown that hematopoietic USF1 deficiency is associated with an increased atherosclerosis susceptibility in LDL receptor knockout mice. These findings argue against a contribution of macrophage-specific USF1 deficiency to the previously described beneficial effect of total body USF1 deficiency on atherosclerosis susceptibility in mice.Menno HoekstraBaoyan RenPirkka-Pekka LaurilaReeni B. HildebrandJarkko SoronenVanessa FrodermannZhuang LiMariëtte R. BoonJanine J. GeerlingPatrick C. N. RensenMatti JauhiainenMiranda Van EckNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Menno Hoekstra Baoyan Ren Pirkka-Pekka Laurila Reeni B. Hildebrand Jarkko Soronen Vanessa Frodermann Zhuang Li Mariëtte R. Boon Janine J. Geerling Patrick C. N. Rensen Matti Jauhiainen Miranda Van Eck Hematopoietic upstream stimulating factor 1 deficiency is associated with increased atherosclerosis susceptibility in LDL receptor knockout mice
description	Abstract Total body upstream stimulatory factor 1 (USF1) deficiency in mice is associated with brown adipose tissue activation and a marked protection against the development of obesity and atherosclerotic lesions. Functional expression of USF1 has also been detected in monocytes and monocyte-derived macrophages. In the current study we therefore tested whether selective hematopoietic USF1 deficiency can also beneficially impact the development of atherosclerosis. For this purpose, LDL receptor knockout mice were transplanted with bone marrow from USF1 knockout mice or their wild-type littermate controls and subsequently fed a Western-type diet for 20 weeks to stimulate atherosclerotic lesion development. Strikingly, absence of USF1 function in bone marrow-derived cells was associated with exacerbated blood leukocyte (+ 100%; P < 0.01) and peritoneal leukocyte (+ 50%; P < 0.05) lipid loading and an increased atherosclerosis susceptibility (+ 31%; P < 0.05). These effects could be attributed to aggravated hyperlipidemia, i.e. higher plasma free cholesterol (+ 33%; P < 0.001) and cholesteryl esters (+ 39%; P < 0.001), and the development of hepatosteatosis. In conclusion, we have shown that hematopoietic USF1 deficiency is associated with an increased atherosclerosis susceptibility in LDL receptor knockout mice. These findings argue against a contribution of macrophage-specific USF1 deficiency to the previously described beneficial effect of total body USF1 deficiency on atherosclerosis susceptibility in mice.
format	article
author	Menno Hoekstra Baoyan Ren Pirkka-Pekka Laurila Reeni B. Hildebrand Jarkko Soronen Vanessa Frodermann Zhuang Li Mariëtte R. Boon Janine J. Geerling Patrick C. N. Rensen Matti Jauhiainen Miranda Van Eck
author_facet	Menno Hoekstra Baoyan Ren Pirkka-Pekka Laurila Reeni B. Hildebrand Jarkko Soronen Vanessa Frodermann Zhuang Li Mariëtte R. Boon Janine J. Geerling Patrick C. N. Rensen Matti Jauhiainen Miranda Van Eck
author_sort	Menno Hoekstra
title	Hematopoietic upstream stimulating factor 1 deficiency is associated with increased atherosclerosis susceptibility in LDL receptor knockout mice
title_short	Hematopoietic upstream stimulating factor 1 deficiency is associated with increased atherosclerosis susceptibility in LDL receptor knockout mice
title_full	Hematopoietic upstream stimulating factor 1 deficiency is associated with increased atherosclerosis susceptibility in LDL receptor knockout mice
title_fullStr	Hematopoietic upstream stimulating factor 1 deficiency is associated with increased atherosclerosis susceptibility in LDL receptor knockout mice
title_full_unstemmed	Hematopoietic upstream stimulating factor 1 deficiency is associated with increased atherosclerosis susceptibility in LDL receptor knockout mice
title_sort	hematopoietic upstream stimulating factor 1 deficiency is associated with increased atherosclerosis susceptibility in ldl receptor knockout mice
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/17a14d3adad549cc9cc447dc81e3bc71
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Hematopoietic upstream stimulating factor 1 deficiency is associated with increased atherosclerosis susceptibility in LDL receptor knockout mice

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