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2017 ; 7
(ä): 46307
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Upregulation of sestrins protect atriums against oxidative damage and fibrosis in
human and experimental atrial fibrillation
#MMPMID28397812
Dong Z
; Lin C
; Liu Y
; Jin H
; Wu H
; Li Z
; Sun L
; Zhang L
; Hu X
; Wei Y
; Wang C
; Han W
Sci Rep
2017[Apr]; 7
(ä): 46307
PMID28397812
show ga
Atrial Fibrillation (AF) is common in the elderly and Sestrins (Sesns) have been
suggested to prevent age-related pathologies. The aim of this study was to
investigate the effects of Sesns in AF. Clinical data were collected and a small
sample of atrial appendage and atrium was obtained from patients undergoing valve
repairment. The expression of Sesn1, Sesn2, and Sesn3 was significantly higher in
patients with permanent atrial fibrillation (PmAF) than that in sinus rhythm
(SR), and further greater in the left atrium than the right in PmAF patients.
Superoxide anion and malondialdehyde were enhanced and positively correlated to
the protein expression of Sesn1/2/3. Reactive oxygen species (ROS) production and
Ca(2+) overload were significantly decreased and cell survival was enhanced by
overexpression of Sesns 1/2/3 in cultured HL-1 cells. Conversely, knockdown of
Sesn1/2/3 resulted in significantly increased ROS and Ca(2+) overload. In
addition, the overexpression of Sesn1/2 significantly reduced the proliferation
of fibroblasts, as well as decreased the protein expression of collagen and
fibronectin1 in angiotensin II-stimulated cardiac fibroblasts. Our study
demonstrated for the first time that Sesns expression is significantly
up-regulated in AF, which therefore may protect hearts against oxidative damage
and atrial fibrosis.