Endothelial protein kinase MAP4K4 promotes vascular inflammation and atherosclerosis

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dc.contributor.authorFlach, Rachel J. Roth
dc.contributor.authorSkoura, Athanasia
dc.contributor.authorHagan, Nana
dc.contributor.authorYawe, Joseph C.
dc.contributor.authorVangala, Pranitha
dc.contributor.authorMenendez, Lorena Garcia
dc.contributor.authorBuckbinder, Leonard
dc.contributor.authorCzech, Michael P.
dc.date.accessioned2023-04-13T15:08:27Z
dc.date.available2023-04-13T15:08:27Z
dc.date.issued2015
dc.description.abstractSignalling pathways that control endothelial cell (EC) permeability, leukocyte adhesion and inflammation are pivotal for atherosclerosis initiation and progression. Here we demonstrate that the Sterile-20-like mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4), which has been implicated in inflammation, is abundantly expressed in ECs and in atherosclerotic plaques from mice and humans. On the basis of endothelial-specific MAP4K4 gene silencing and gene ablation experiments in Apoe−/− mice, we show that MAP4K4 in ECs markedly promotes Western diet-induced aortic macrophage accumulation and atherosclerotic plaque development. Treatment of Apoe−/− and Ldlr−/− mice with a selective small-molecule MAP4K4 inhibitor also markedly reduces atherosclerotic lesion area. MAP4K4 silencing in cultured ECs attenuates cell surface adhesion molecule expression while reducing nuclear localization and activity of NFκB, which is critical for promoting EC activation and atherosclerosis. Taken together, these results reveal that MAP4K4 is a key signalling node that promotes immune cell recruitment in atherosclerosis.en_US
dc.identifier.citationRoth Flach, R. J., Skoura, A., Matevossian, A., Danai, L. V., Zheng, W., Cortes, C., ... & Czech, M. P. (2015). Endothelial protein kinase MAP4K4 promotes vascular inflammation and atherosclerosis. Nature communications, 6(1), 8995.https://doi.org/10.1038/ncomms9995en_US
dc.identifier.issn2041-1723
dc.identifier.urihttps://nru.uncst.go.ug/handle/123456789/8452
dc.language.isoenen_US
dc.publisherNature communicationsen_US
dc.subjectAtherosclerosisen_US
dc.subjectEndothelial protein kinaseen_US
dc.subjectVascular inflammationen_US
dc.titleEndothelial protein kinase MAP4K4 promotes vascular inflammation and atherosclerosisen_US
dc.typeArticleen_US
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