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          Institute: MPI für molekulare Biomedizin     Collection: Jahrbuch 2017 (publ. 2016, arch)     Display Documents



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ID: 732138.0, MPI für molekulare Biomedizin / Jahrbuch 2017 (publ. 2016, arch)
Stability and function of adult vasculature is sustained by Akt/Jagged1 signalling axis in endothelium
Authors:Kerr, B. A.; West, X. Z.; Kim, Y. W.; Zhao, Y. Z.; Tischenko, M.; Cull, R. M.; Phares, T. W.; Peng, X. D.; Bernier-Latmani, J.; Petrova, T. V.; Adams, R. H.; Hay, N.; Prasad, S. V. N.; Byzova, T. V.
Date of Publication (YYYY-MM-DD):2016-03
Title of Journal:Nat Commun
Volume:7
Start Page:18
Review Status:Internal review
Audience:Not Specified
Abstract / Description:The signalling pathways operational in quiescent, post-development vasculature remain enigmatic. Here we show that unlike neovascularization, endothelial Akt signalling in established vasculature is crucial not for endothelial cell (EC) survival, but for sustained interactions with pericytes and vascular smooth muscle cells (VSMCs) regulating vascular stability and function. Inducible endothelial-specific Akt1 deletion in adult global Akt2KO mice triggers progressive VSMC apoptosis. In hearts, this causes a loss of arteries and arterioles and, despite a high capillary density, diminished vascular patency and severe cardiac dysfunction. Similarly, endothelial Akt deletion induces retinal VSMC loss and basement membrane deterioration resulting in vascular regression and retinal atrophy. Mechanistically, the Akt/mTOR axis controls endothelial Jagged1 expression and, thereby, Notch signalling regulating VSMC maintenance. Jagged1 peptide treatment of Akt1 Delta EC; Akt2KO mice and Jagged1 re-expression in Akt-deficient endothelium restores VSMC coverage. Thus, sustained endothelial Akt1/2 signalling is critical in maintaining vascular stability and homeostasis, thereby preserving tissue and organ function.
Free Keywords:inhibits tumor-growth; pathological angiogenesis; cardiovascular-disease; p110-alpha isoform; clinical-trial; in-vivo; akt; notch; cell; jagged1; Science & Technology - Other Topics
External Publication Status:published
Document Type:Article
Communicated by:Jeanine Müller-Keuker
Affiliations:MPI für molekulare Biomedizin
External Affiliations:Byzova, TV (reprint author), Cleveland Clin, Dept Mol Cardiol, Joseph J Jacobs Ctr Thrombosis & Vasc Biol, Lerner Res Inst, Cleveland, OH 44195 USA. byzovat@ccf.org %G English
Identifiers:ISSN:2041-1723 %R 10.1038/ncomms10960 %] 10960 [ID No:1]
URL:<Go to ISI>://WOS:000372186700001 [ID No:2]
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