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

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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

Title: Hematopoietic upstream stimulating factor 1 deficiency is associated with increased atherosclerosis susceptibility in LDL receptor knockout mice
Author: Hoekstra, Menno; Ren, Baoyan; Laurila, Pirkka-Pekka; Hildebrand, Reeni B.; Soronen, Jarkko; Frodermann, Vanessa; Li, Zhuang; Boon, Mariette R.; Geerling, Janine J.; Rensen, Patrick C. N.; Jauhiainen, Matti; Van Eck, Miranda
Other contributor: University of Helsinki, Department of Medical and Clinical Genetics

Date: 2021-08-12
Language: eng
Number of pages: 11
Belongs to series: Scientific Reports
ISSN: 2045-2322
DOI: https://doi.org/10.1038/s41598-021-95858-y
URI: http://hdl.handle.net/10138/335064
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.
Subject: FATTY LIVER-DISEASE
TRANSCRIPTION FACTOR
ALLELIC VARIANTS
FACTOR BINDS
GENE
PROMOTER
USF1
CHOLESTEROL
MACROPHAGES
ELEMENT
3111 Biomedicine
1184 Genetics, developmental biology, physiology
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