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• W2949852046 endingPage "172442" @default.
• W2949852046 startingPage "172442" @default.
• W2949852046 abstract "Cardiac dysfunction is a pathological state characterized by damaged ability of the left ventricle (LV) to either eject or fill blood accompanied by cardiac hypertrophy and fibrosis. IMM-H007, an adenosine derivative, is an activator of AMP-Activated Protein Kinase (AMPK). AMPK can decrease the transforming growth factor-β1 (TGF-β1) expression during fibrosis. Therefore, we hypothesized that IMM-H007 contributed to cardiac dysfunction by mediating cardiac fibrosis. To test this hypothesis, we used angiotensin II (AngII)-induced cardiac remodeling model treated with IMM-H007 or vehicle. Echocardiography measurements showed that IMM-H007 significantly improved heart function indicated by increased LV ejection fraction (%LVEF) and LV fractional shortening (%LVFS). Histological staining and qRT-PCR analysis revealed that IMM-H007 markedly reduced AngII-induced cardiac fibroblast activation (α-smooth muscle actin and periostin) and matrix protein production (Collagen I and Collagen III). However, IMM-H007 did not affect AngII-induced cardiac hypertrophy. Immunoblotting analysis revealed that IMM-H007 activated AMPK, decreased the expression of TGF-β1, and inhibited the activation of Smad2 in heart tissues. In mouse primary cultured cardiac fibroblasts, pharmacological activation of AMPK by IMM-H007 significantly reduced AngII-induced TGF-β1 expression as well. Consistently, in human cardiac fibroblasts-adult ventricular (HCF-av), IMM-H007 activated AMPK and markedly suppressed AngII-induced TGF-β1 expression. These results together reveal that IMM-H007 improves heart function, and alleviates AngII-induced cardiac fibrosis by regulating AMPK-TGF-β1 signaling. These findings suggest IMM-H007 as a potential drug for treating cardiac dysfunction." @default.
• W2949852046 created "2019-06-27" @default.
• W2949852046 creator A5003599636 @default.
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• W2949852046 date "2019-08-01" @default.
• W2949852046 modified "2023-10-14" @default.
• W2949852046 title "IMM-H007 improves heart function via reducing cardiac fibrosis" @default.
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• W2949852046 doi "https://doi.org/10.1016/j.ejphar.2019.172442" @default.
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• W2949852046 hasPublicationYear "2019" @default.
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