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N‐acetylcysteine Ameliorates Infarction‐induced Myocardial Fibrosis
Author(s) -
Lee Tsung-Ming,
Chen Chien-Chang
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.1133.1
Subject(s) - rhoa , acetylcysteine , fasudil , fibrosis , chemistry , ctgf , connective tissue , myocardial infarction , pharmacology , medicine , rho associated protein kinase , biochemistry , growth factor , pathology , kinase , signal transduction , antioxidant , receptor
Excessive production and deposition of extracellular matrix proteins is a feature after myocardial infarction. Reactive oxygen species contributes to collagen synthesis through the activation of RhoA. We assessed whether N‐acetylcysteine could attenuate myocardial fibrosis after myocardial infarction. Male Wistar rats after ligating coronary artery were randomized to either vehicle, or N‐acetylcysteine for 4 weeks. Post‐infarction was associated with increased oxidant release, as measured by myocardial glutathione and superoxide, and dihydroethidium fluorescent staining. RhoA/ROCK activation after infarction was observed by increasing RhoA localization from the cytosol to the membrane and phosphorylating the ROCK substrate myosin phosphatase target subunit 1. N‐acetylcysteine diminished myocardial fibrosis by inhibiting RhoA/ROCK activation without alteration of TGF‐β1 proteins. A Rho inhibitor, C3 exoenzyme, and 2 ROCK inhibitors, fasudil and Y‐27632, significantly attenuated connective tissue growth factor expression. Furthermore, the effects of N‐acetylcysteine on connective tissue growth factor were abolished by administering L‐buthionine sulfoximinem. These results indicate that N‐acetylcysteine as a glutathione precursor can expedite the attenuation of infarction‐induced myocardial fibrosis probably through the inhibition of TGF‐β1‐indepdent RhoA/ROCK activity.