Endothelial Cell Autonomous Role of Akt1: Regulation of Vascular Tone and Ischemia-Induced Arteriogenesis

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

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34 Citas (Scopus)

Resumen

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.

Idioma originalEnglish
Páginas (desde-hasta)870-879
Número de páginas10
PublicaciónArteriosclerosis, Thrombosis, and Vascular Biology
Volumen38
N.º4
DOI
EstadoPublished - 1 abr 2018
Publicado de forma externa

Nota bibliográfica

Publisher Copyright:
© 2018 American Heart Association, Inc.

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