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Vasculopathy-associated hyperangiotensinemia mobilizes haematopoietic stem
cells/progenitors through endothelial AT?R and cytoskeletal dysregulation
#MMPMID25574809
Chang KH
; Nayak RC
; Roy S
; Perumbeti A
; Wellendorf AM
; Bezold KY
; Pirman M
; Hill SE
; Starnes J
; Loberg A
; Zhou X
; Inagami T
; Zheng Y
; Malik P
; Cancelas JA
Nat Commun
2015[Jan]; 6
(?): 5914
PMID25574809
show ga
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.
|Actins/metabolism
[MESH]
|Adaptor Proteins, Signal Transducing/genetics/*metabolism
[MESH]
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