The Nuclear Factor-kappa B p50 subunit is involved in flow-induced outward arterial remodeling

AimsOutward 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-κB) that controls the transcription of many inflammatory genes. The NF-κB subunit p50 is generally considered to be an inhibitory subunit of the NF-κB complex. We therefore hypothesize that NF-κB p50 inhibits outward arterial remodeling.Methods and resultsCarotid artery ligation in mice, induced outward remodeling in contralateral arteries of NF-κB p50−/− (p50−/−) and wild type (WT) arteries. p50−/− arteries showed more outward arterial remodeling than WT arteries (19894.0 ± 3136.7 μm2 vs. 6120.7 ± 2741.2 μm2, 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.ConclusionsThe NF-κB 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-κB subunit p50.