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• W2885836788 abstract "Follistatin-like 1 (Fstl1) protects cardiomyocytes from a broad spectrum of pathologic injuries including myocardial infarction (MI). It is worthy of note that although cardiac Fstl1 is elevated in post-MI microenvironment, its cardioprotective role is still restricted to a limited extent considering the frequency and severity of adverse cardiac remodeling following MI. We therefore propose that intrinsic Fstl1-suppressing microRNA (miRNA) may exist in the heart and its neutralization may further facilitate post-MI recovery. Here, miR-9-5p is predicted as one of the potential Fstl1-targeting miRNAs whose expression is decreased in ischemic myocardium and reversely correlated with Fstl1. Luciferase activity assay further validated Fstl1 as a direct target of miR-9-5p. In addition, forced expression of miR-9-5p in H9c2 cells is concurrent with diminished expression of Fstl1 and vice versa. Importantly, transfection of miR-9-5p mimics in hypoxic H9c2 cells exacerbates cardiac cell death, lactate dehydrogenase release, reactive oxygen species accumulation, and malonyldialdehyde concentration. More importantly, in vivo silencing of miR-9-5p by a specific antagomir in a murine acute MI model effectively preserves post-MI heart function with attenuated fibrosis and inflammatory response. Further studies demonstrated that antagomir treatment stabilizes Fstl1 expression as well as blocks cardiac cell death and reactive oxygen species generation in both ischemia-challenged hearts and hypoxia-treated cardiomyoblasts. Finally, cytoprotection against hypoxic challenge by miR-9-5p inhibitor is partially reversed by knockdown of Fstl1, indicating a novel role of miR-9-5p/Fstl1 axis in survival defense against hypoxic challenge. In summary, these findings identified miR-9-5p as a mediator of hypoxic injury in cardiomyoblasts and miR-9-5p suppression prevents cardiac remodeling after acute MI, providing a potential strategy for early treatment against MI." @default.
• W2885836788 created "2018-08-22" @default.
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• W2885836788 date "2019-03-01" @default.
• W2885836788 modified "2023-10-13" @default.
• W2885836788 title "Inhibition of MicroRNA-9-5p Protects Against Cardiac Remodeling Following Myocardial Infarction in Mice" @default.
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• W2885836788 doi "https://doi.org/10.1089/hum.2018.059" @default.
• W2885836788 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30101604" @default.
• W2885836788 hasPublicationYear "2019" @default.
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