TY - JOUR
T1 - Endothelial Cell Autonomous Role of Akt1
T2 - Regulation of Vascular Tone and Ischemia-Induced Arteriogenesis
AU - Lee, Monica Y
AU - Gamez-Mendez, Ana
AU - Zhang, Jiasheng
AU - Zhuang, Zhenwu
AU - Vinyard, David J
AU - Kraehling, Jan
AU - Velazquez, Heino
AU - Brudvig, Gary W
AU - Kyriakides, Themis R
AU - Simons, Michael
AU - Sessa, William C
N1 - Funding Information:
This work was supported by Grants R01 HL64793, R01 HL61371, R01 HL081190, R35 HL139945 (to W.C. Sessa), the Leducq Fondation (MIRVAD network; to W.C. Sessa), AHA MERIT Award (to W.C. Sessa), RO1 HL053793 (to M. Simons), P01 HL70295 (to M. Simons and W.C. Sessa), HL 1K99HL130581-01 to M.Y. Lee, RO1 GM072194 to T.R. Kyriakides, and the George M O’Brian Kidney Center at Yale, NIH grant P30DK079310 to H. Velazquez from the National Institutes of Health.
Publisher Copyright:
© 2018 American Heart Association, Inc.
PY - 2018/4/1
Y1 - 2018/4/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85044362031&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85044362031&partnerID=8YFLogxK
UR - https://www.mendeley.com/catalogue/77b5efb0-483b-3116-924c-07b82895ab59/
U2 - 10.1161/ATVBAHA.118.310748
DO - 10.1161/ATVBAHA.118.310748
M3 - Article
C2 - 29449333
SN - 1079-5642
VL - 38
SP - 870
EP - 879
JO - Arteriosclerosis, Thrombosis, and Vascular Biology
JF - Arteriosclerosis, Thrombosis, and Vascular Biology
IS - 4
ER -