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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Arterioscler+Thromb+Vasc+Biol
2012 ; 32
(12
): 3012-23
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gab.com Text
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English Wikipedia
Inhibition of Notch1 signaling reduces abdominal aortic aneurysm in mice by
attenuating macrophage-mediated inflammation
#MMPMID23087364
Hans CP
; Koenig SN
; Huang N
; Cheng J
; Beceiro S
; Guggilam A
; Kuivaniemi H
; Partida-Sánchez S
; Garg V
Arterioscler Thromb Vasc Biol
2012[Dec]; 32
(12
): 3012-23
PMID23087364
show ga
OBJECTIVE: Activation of inflammatory pathways plays a critical role in the
development of abdominal aortic aneurysms (AAA). Notch1 signaling is a
significant regulator of the inflammatory response; however, its role in AAA is
unknown. METHODS AND RESULTS: In an angiotensin II-induced mouse model of AAA,
activation of Notch1 signaling was observed in the aortic aneurysmal tissue of
Apoe(-/-) mice, and a similar activation of Notch1 was observed in aneurysms of
humans undergoing AAA repair. Notch1 haploinsufficiency significantly reduced the
incidence of AAA in Apoe(-/-) mice in response to angiotensin II. Reconstitution
of bone marrow-derived cells from Notch1(+/-);Apoe(-/-) mice (donor) in lethally
irradiated Apoe(-/-) mice (recipient) decreased the occurrence of aneurysm. Flow
cytometry and immunohistochemistry demonstrated that Notch1 haploinsufficiency
prevented the influx of inflammatory macrophages at the aneurysmal site by
causing defects in macrophage migration and proliferation. In addition, there was
an overall reduction in the inflammatory burden in the aorta of the
Notch1(+/-);Apoe(-/-) mice compared with the Apoe(-/-) mice. Last,
pharmacological inhibition of Notch1 signaling also prevented AAA formation and
progression in Apoe(-/-) mice. CONCLUSIONS: Our data suggest that decreased
levels of Notch1 protect against the formation of AAA by preventing macrophage
recruitment and attenuating the inflammatory response in the aorta.
|Angiotensin II/adverse effects
[MESH]
|Animals
[MESH]
|Aortic Aneurysm, Abdominal/chemically induced/physiopathology/*prevention &
control
[MESH]
free
free
free
