کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
8473713 1550408 2016 36 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Metformin inhibits aldosterone-induced cardiac fibroblast activation, migration and proliferation in vitro, and reverses aldosterone + salt-induced cardiac fibrosis in vivo
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیولوژی سلول
پیش نمایش صفحه اول مقاله
Metformin inhibits aldosterone-induced cardiac fibroblast activation, migration and proliferation in vitro, and reverses aldosterone + salt-induced cardiac fibrosis in vivo
چکیده انگلیسی
The overall goals of this study were to investigate whether metformin exerts anti-fibrotic effects in aldosterone (Aldo) + salt-treated wild type mouse hearts, and determine the underlying molecular mechanisms in isolated adult cardiac fibroblasts (CF). In vitro, Aldo induced CF activation, migration, and proliferation, and these effects were inhibited by metformin. Further, Aldo induced PPM1A (Protein Phosphatase Magnesium Dependent 1A) activation and inhibited AMPK phosphorylation. At a pharmacologically relevant concentration, metformin restored AMPK activation, and inhibited Aldo-induced Nox4/H2O2-dependent TRAF3IP2 induction, pro-inflammatory cytokine expression, and CF migration and proliferation. Further, metformin potentiated the inhibitory effects of spironolactone, a mineralocorticoid receptor antagonist, on Aldo-induced collagen expression, and CF migration and proliferation. These results were recapitulated in vivo, where metformin reversed Aldo + salt-induced oxidative stress, suppression of AMPK activation, TRAF3IP2 induction, pro-inflammatory cytokine expression, and cardiac fibrosis, without significantly modulating systolic blood pressure. These in vitro and in vivo data indicate that metformin has the potential to reduce adverse cardiac remodeling in hypertensive heart disease.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Molecular and Cellular Cardiology - Volume 98, September 2016, Pages 95-102
نویسندگان
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