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Filtering by: Creator/Author Wellendorf, A. M. Department Hoxworth Blood Center

Vasculopathy associated hyperangiotensinemia mobilizes hematopoietic stem cells/progenitors through endothelial AT2R and cytoskeletal dysregulation

Type:

Article

Description/Abstract:

Patients in organ failure of vascular origin have increased circulating hematopoietic stem cells and progenitors (HSC/P). Plasma levels of angiotensin II (Ang-II), are commonly increased in vasculopathies. Hyperangiotensinemia results in activation of a very distinct Ang-II receptor set, Rho-family GTPase members, and actin in bone marrow endothelial cells (BMEC) and HSC/P, which results in decreased membrane integrin activation in both BMEC and HSC/P, and in HSC/P de-adhesion and mobilization. The Ang-II effect can be reversed pharmacologically and genetically by inhibiting Ang-II production or signaling through BMEC AT2R, HSCP AT1R/ AT2R or HSC/P RhoA, but not by interfering with other vascular tone mediators. Hyperangiotensinemia and high counts of circulating HSC/P seen in sickle cell disease (SCD) as a result of vascular damage, is significantly decreased by Ang-II inhibitors. Our data define for the first time the role of Ang-II HSC/P traffic regulation and redefine the hematopoietic consequences of anti-angiotensin therapy in SCD.

Creator/Author:

Inagami, T.; Hill, S. E.; Wellendorf, A. M.; Perumbeti, A.; Nayak, R. C.; Bezold, K. Y.; Zheng, Y.; Chang, K. H.; Pirman, M.; Loberg, A.; Cancelas, Jose A.; Roy, S.; Malik, P.; Starnes, J., and Zhou, X.

Submitter:

Jose Cancelas

Date Uploaded:

02/08/2017

Date Modified:

04/10/2017

Date Created:

2015-01

License:

All rights reserved

Vasculopathy associated hyperangiotensinemia mobilizes hematopoietic stem cells/progenitors through endothelial AT2R and cytoskeletal dysregulation

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Vasculopathy associated hyperangiotensinemia mobilizes hematopoietic stem cells/progenitors through endothelial AT2R and cytoskeletal dysregulation

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