Hematopoietic NF-κB1 deficiency results in small atherosclerotic lesions with an inflammatory phenotype
- 1 February 2004
- journal article
- Published by American Society of Hematology in Blood
- Vol. 103 (3), 934-940
- https://doi.org/10.1182/blood-2003-05-1450
Abstract
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 κB (NF-κB), and we have studied its role in the development of atherosclerosis. Bone marrow from mice targeted in the NF-κB1 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-κB1 had a 41% lower rate of atherosclerosis than control mice, as judged by the sizes of the lesions. Furthermore, in the absence of NF-κB1, 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. (Blood. 2004;103:934-940)Keywords
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