N-acetylcysteine attenuates the development of cardiac fibrosis and remodeling in a mouse model of heart failure

Beverly Giam, Po - Yin Chu, Sanjaya Kuruppu, A. Ian Smith, Duncan Horlock, Helen Kiriazis, Xiao-Jun Du, David M. Kaye, Niwanthi W. Rajapakse

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19 Citations (Scopus)

Abstract

Oxidative stress plays a central role in the pathogenesis of heart failure. We aimed to determine whether the antioxidant N-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 administer N-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 and III were quantified in heart tissues. Cardiac perivascular and interstitial fibrosis were greater by 114% and 209%, respectively, in MST-1 compared to wild type (P ≤ 0.001). In MST-1 mice administered N-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 in MST-1 than in wild type (P < 0.001) and N-acetylcysteine attenuated oxidative stress in MST-1 by 42% (P = 0.005). These data indicate that N-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 of N-acetylcysteine in chronic heart failure.

Original languageEnglish
Article numbere12757
Number of pages13
JournalPhysiological Reports
Volume4
Issue number7
DOIs
Publication statusPublished - 1 Apr 2016

Keywords

  • Fibrosis
  • Heart failure
  • N-acetylcysteine
  • Oxidative stress

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