Endothelial Cell Autonomous Role of Akt1

Monica Y. Lee, Ana Gamez-Mendez, Jiasheng Zhang, Zhenwu Zhuang, David J. Vinyard, Jan Kraehling, Heino Velazquez, Gary W. Brudvig, Themis R. Kyriakides, Michael Simons, William C. Sessa

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Objective - The importance of PI3K/Akt signaling in the vasculature has been demonstrated in several models, as global loss of Akt1 results in impaired postnatal ischemia- and VEGF-induced angiogenesis. The ubiquitous expression of Akt1, however, raises the possibility of cell-type-dependent Akt1-driven actions, thereby necessitating tissue-specific characterization. Approach and Results - Herein, we used an inducible, endothelial-specific Akt1-deleted adult mouse model (Akt1iECKO) to characterize the endothelial cell autonomous functions of Akt1 in the vascular system. Endothelial-targeted ablation of Akt1 reduces eNOS (endothelial nitric oxide synthase) phosphorylation and promotes both increased vascular contractility in isolated vessels and elevated diastolic blood pressures throughout the diurnal cycle in vivo. Furthermore, Akt1iECKO mice subject to the hindlimb ischemia model display impaired blood flow and decreased arteriogenesis. Conclusions - Endothelial Akt1 signaling is necessary for ischemic resolution post-injury and likely reflects the consequence of NO insufficiency critical for vascular repair.

Original languageEnglish
Pages (from-to)870-879
Number of pages10
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume38
Issue number4
DOIs
Publication statusPublished - Apr 1 2018

Keywords

  • blood pressure
  • endothelial cell
  • hindlimb
  • homeostasis
  • phosphorylation

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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    Lee, M. Y., Gamez-Mendez, A., Zhang, J., Zhuang, Z., Vinyard, D. J., Kraehling, J., Velazquez, H., Brudvig, G. W., Kyriakides, T. R., Simons, M., & Sessa, W. C. (2018). Endothelial Cell Autonomous Role of Akt1. Arteriosclerosis, Thrombosis, and Vascular Biology, 38(4), 870-879. https://doi.org/10.1161/ATVBAHA.118.310748