N-acetylcysteine attenuates the development of cardiac fibrosis and remodeling in
a mouse model of heart failure
#MMPMID27081162
Giam B
; Chu PY
; Kuruppu S
; Smith AI
; Horlock D
; Kiriazis H
; Du XJ
; Kaye DM
; Rajapakse NW
Physiol Rep
2016[Apr]; 4
(7
): ? PMID27081162
show ga
Oxidative stress plays a central role in the pathogenesis of heart failure. We
aimed to determine whether the antioxidantN-acetylcysteine can attenuate cardiac
fibrosis and remodeling in a mouse model of heart failure. Minipumps were
implanted subcutaneously in wild-type mice (n = 20) and mice with cardiomyopathy
secondary to cardiac specific overexpression of mammalian sterile 20-like kinase
1 (MST-1;n = 18) to administerN-acetylcysteine (40 mg/kg per day) or saline for a
period of 8 weeks. At the end of this period, cardiac remodeling and function was
assessed via echocardiography. Fibrosis, oxidative stress, and expression of
collagen types I andIIIwere quantified in heart tissues. Cardiac perivascular and
interstitial fibrosis were greater by 114% and 209%, respectively, inMST-1
compared to wild type (P ? 0.001). InMST-1 mice administeredN-acetylcysteine,
perivascular and interstitial fibrosis were 40% and 57% less, respectively,
compared to those treated with saline (P ? 0. 03). Cardiac oxidative stress was
119% greater inMST-1 than in wild type (P < 0.001) andN-acetylcysteine attenuated
oxidative stress inMST-1 by 42% (P = 0.005). These data indicate
thatN-acetylcysteine can blunt cardiac fibrosis and related remodeling in the
setting of heart failure potentially by reducing oxidative stress. This study
provides the basis to investigate the role ofN-acetylcysteine in chronic heart
failure.
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