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

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dc.contributor.author Hoekstra, Menno
dc.contributor.author Ren, Baoyan
dc.contributor.author Laurila, Pirkka-Pekka
dc.contributor.author Hildebrand, Reeni B.
dc.contributor.author Soronen, Jarkko
dc.contributor.author Frodermann, Vanessa
dc.contributor.author Li, Zhuang
dc.contributor.author Boon, Mariette R.
dc.contributor.author Geerling, Janine J.
dc.contributor.author Rensen, Patrick C. N.
dc.contributor.author Jauhiainen, Matti
dc.contributor.author Van Eck, Miranda
dc.date.accessioned 2021-10-08T05:35:02Z
dc.date.available 2021-10-08T05:35:02Z
dc.date.issued 2021-08-12
dc.identifier.citation Hoekstra , M , Ren , B , Laurila , P-P , Hildebrand , R B , Soronen , J , Frodermann , V , Li , Z , Boon , M R , Geerling , J J , Rensen , P C N , Jauhiainen , M & Van Eck , M 2021 , ' Hematopoietic upstream stimulating factor 1 deficiency is associated with increased atherosclerosis susceptibility in LDL receptor knockout mice ' , Scientific Reports , vol. 11 , no. 1 , 16419 . https://doi.org/10.1038/s41598-021-95858-y
dc.identifier.other PURE: 169262635
dc.identifier.other PURE UUID: 9ffd868f-8ba7-4302-981e-42923f0e6e63
dc.identifier.other WOS: 000686909600026
dc.identifier.uri http://hdl.handle.net/10138/335064
dc.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. en
dc.format.extent 11
dc.language.iso eng
dc.relation.ispartof Scientific Reports
dc.rights cc_by
dc.rights.uri info:eu-repo/semantics/openAccess
dc.subject FATTY LIVER-DISEASE
dc.subject TRANSCRIPTION FACTOR
dc.subject ALLELIC VARIANTS
dc.subject FACTOR BINDS
dc.subject GENE
dc.subject PROMOTER
dc.subject USF1
dc.subject CHOLESTEROL
dc.subject MACROPHAGES
dc.subject ELEMENT
dc.subject 3111 Biomedicine
dc.subject 1184 Genetics, developmental biology, physiology
dc.title Hematopoietic upstream stimulating factor 1 deficiency is associated with increased atherosclerosis susceptibility in LDL receptor knockout mice en
dc.type Article
dc.contributor.organization Department of Medical and Clinical Genetics
dc.contributor.organization Faculty of Medicine
dc.description.reviewstatus Peer reviewed
dc.relation.doi https://doi.org/10.1038/s41598-021-95858-y
dc.relation.issn 2045-2322
dc.rights.accesslevel openAccess
dc.type.version publishedVersion

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