Hematopoietic NF-kappaB1 deficiency results in small atherosclerotic lesions with an inflammatory phenotype.

E. Kanters, M.J.J. Gijbels, I. van der Made, M.N. Vergouwe, P. Heeringa, G. Kraal, M.H. Hofker, M.P.J. de Winther

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Abstract

Hematopoietic NF-kappaB1 deficiency results in small atherosclerotic lesions with an inflammatory phenotype.

Kanters E, Gijbels MJ, van der Made I, Vergouwe MN, Heeringa P, Kraal G, Hofker MH, de Winther MP.

Department of Molecular Genetics, Cardiovascular Research Institute Maastricht UNS50/11, Universiteitssingel 50, 6229ER Maastricht, The Netherlands.

Atherosclerosis is a chronic inflammatory disease characterized by the accumulation of lipid-laden macrophages in the vessel wall. One of the major transcription factors in inflammation is nuclear factor kappaB (NF-kappaB), and we have studied its role in the development of atherosclerosis. Bone marrow from mice targeted in the NF-kappaB1 gene encoding for the p50 subunit was used to reconstitute irradiated LDLR(-/-) mice as a model for atherosclerosis. After feeding the mice a high-fat diet, those deficient in NF-kappaB1 had a 41% lower rate of atherosclerosis than control mice, as judged by the sizes of the lesions. Furthermore, in the absence of NF-kappaB1, the lesions were characterized by an inflammatory phenotype, contained increased numbers of small cells, and were almost devoid of normal foam cells. In vitro studies using bone marrow (BM)-derived macrophages showed that macrophages lacking p50 had a prolonged production of tumor necrosis factor (TNF) in response to lipopolysaccharide (LPS), and other cytokines were also affected. Interestingly, the uptake of oxidized low-density lipoprotein (LDL) was greatly reduced in activated p50-deficient macrophages, probably because of a reduction in the expression of scavenger receptor class A. The effects on atherosclerosis might have resulted from the changes in cytokine production and the uptake of modified lipoproteins, making p50 a pivotal regulator of atherogenesis
Original languageEnglish
Pages (from-to)934-940
Number of pages6
JournalBlood
Volume103
Issue number3
DOIs
Publication statusPublished - 1 Jan 2004

Cite this

Kanters, E., Gijbels, M. J. J., van der Made, I., Vergouwe, M. N., Heeringa, P., Kraal, G., Hofker, M. H., & de Winther, M. P. J. (2004). Hematopoietic NF-kappaB1 deficiency results in small atherosclerotic lesions with an inflammatory phenotype. Blood, 103(3), 934-940. https://doi.org/10.1182/blood-2003-05-1450