The nuclear factor-kappa B p50 subunit is involved in flow-induced outward arterial remodeling

Aims: Outward arterial remodeling is a structural enlargement of the artery that is associated with unstable inflammatory atherosclerotic lesions. Toll-like receptor (Tlr) activation is known as a key pathway in outward arterial remodeling. Tlr activation results in nuclear translocation of the transcription factor Nuclear Factor-kappa B (NF-B) that controls the transcription of many inflammatory genes. The NF-B subunit p50 is generally considered to be an inhibitory subunit of the NF-B complex. We therefore hypothesize that NF-B p50 inhibits outward arterial remodeling. Methods and results: Carotid artery ligation in mice, induced outward remodeling in contralateral arteries of NF-B p50 −/− (p50 −/− ) and wild type (WT) arteries. p50 −/− arteries showed more outward arterial remodeling than WT arteries (19894.0 ± 3136.7m 2 vs. 6120.7 ± 2741.2m 2 , respectively, P = 0.006). In vitro, lipopolysaccharide induced higher cytokine expression levels in p50 −/− cells compared to WT cells. In vivo, more outward remodeling in p50 −/− arteries was associated with a decrease in collagen density and an increased influx of macrophages. Conclusions: The NF-B p50 subunit is involved in outward arterial remodeling. This is probably due to modulation of macrophage influx and adventitial collagen, leading to enhanced flow-induced outward arterial remodeling after targeted deletion of NF-B subunit p50. © 2008 Elsevier Ireland Ltd. All rights reserved.