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

Kyung Hee Chang, Ramesh C Nayak, Swarnava Roy, Ajay Perumbeti, Ashley M Wellendorf, Katie Y Bezold, Megan Pirman, Sarah E Hill, Joseph Starnes, Anastacia Loberg, Xuan Zhou, Tadashi Inagami, Yi Zheng, Punam Malik () and Jose A Cancelas ()
Additional contact information
Kyung Hee Chang: Hoxworth Blood Center, University of Cincinnati College of Medicine
Ramesh C Nayak: Cincinnati Children’s Hospital Medical Center
Swarnava Roy: Cincinnati Children’s Hospital Medical Center
Ajay Perumbeti: Hoxworth Blood Center, University of Cincinnati College of Medicine
Ashley M Wellendorf: Cincinnati Children’s Hospital Medical Center
Katie Y Bezold: Cincinnati Children’s Hospital Medical Center
Megan Pirman: Hoxworth Blood Center, University of Cincinnati College of Medicine
Sarah E Hill: Hoxworth Blood Center, University of Cincinnati College of Medicine
Joseph Starnes: Cincinnati Children’s Hospital Medical Center
Anastacia Loberg: Cincinnati Children’s Hospital Medical Center
Xuan Zhou: Cincinnati Children’s Hospital Medical Center
Tadashi Inagami: Vanderbilt University School of Medicine
Yi Zheng: Cincinnati Children’s Hospital Medical Center
Punam Malik: Cincinnati Children’s Hospital Medical Center
Jose A Cancelas: Hoxworth Blood Center, University of Cincinnati College of Medicine

Nature Communications, 2015, vol. 6, issue 1, 1-11

Abstract: Abstract Patients with organ failure of vascular origin have increased circulating haematopoietic 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 signalling through BMEC AT2R, HSCP Ang-II receptor type 1 (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 haematopoietic consequences of anti-angiotensin therapy in SCD.

Date: 2015
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/ncomms6914 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms6914

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms6914

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().