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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
2017 ; 37
(4
): 694-706
Nephropedia Template TP
gab.com Text
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English Wikipedia
NLRP3 (Nucleotide Oligomerization Domain-Like Receptor Family, Pyrin Domain
Containing 3)-Caspase-1 Inflammasome Degrades Contractile Proteins: Implications
for Aortic Biomechanical Dysfunction and Aneurysm and Dissection Formation
#MMPMID28153878
Wu D
; Ren P
; Zheng Y
; Zhang L
; Xu G
; Xie W
; Lloyd EE
; Zhang S
; Zhang Q
; Curci JA
; Coselli JS
; Milewicz DM
; Shen YH
; LeMaire SA
Arterioscler Thromb Vasc Biol
2017[Apr]; 37
(4
): 694-706
PMID28153878
show ga
OBJECTIVE: Increasing evidence suggests that contractile dysfunction in smooth
muscle cells (SMCs) plays a critical role in aortic biomechanical dysfunction and
aortic aneurysm and dissection (AAD) development. However, the mechanisms
underlying SMC contractile dysfunction in sporadic AAD are poorly understood. In
this study, we examined the role of the NLRP3 (nucleotide oligomerization
domain-like receptor family, pyrin domain containing 3)-caspase-1 inflammasome, a
key inflammatory cascade, in SMC contractile dysfunction in AAD. APPROACH AND
RESULTS: We observed significant SMC contractile protein degradation in aortas
from patients with sporadic thoracic AAD. The contractile protein degradation was
associated with activation of the NLRP3-caspase-1 inflammasome cascade. In SMCs,
caspase-1 bound and directly cleaved and degraded contractile proteins, leading
to contractile dysfunction. Furthermore, Nlrp3 or caspase-1 deficiency in mice
significantly reduced angiotensin II-induced contractile protein degradation,
biomechanical dysfunction, and AAD formation in both thoracic and abdominal
aortas. Finally, blocking this cascade with the inflammasome inhibitor, glyburide
(an antidiabetic medication), reduced angiotensin II-induced AAD formation.
CONCLUSIONS: Inflammasome-caspase-1-mediated degradation of SMC contractile
proteins may contribute to aortic biomechanical dysfunction and AAD development.
This cascade may be a therapeutic target in AAD formation. In addition, glyburide
may have protective effects against AAD development.