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• W4313447962 abstract "Abstract Background: Previous studies found that the myocardial function is damaged in obese mice induced by a high-fat diet, with the increased miRNA-208a and decreased IRS-2. Method: Herein, miR-208a(-/-) knockout and C57BL/6J wild-type mice were divided into the normal diet and high‑fat diet groups, separately. Expressions of p-IRS-2, PI3K, p-AKT, NPPA, AKT, IRS-2, MYH6, MYH7 and Glut4 were determined using immunohistochemical staining. Furthermore, western blotting was performed to identify proteins. Cardiomyocytes were isolated from neonatal rats, and the cardiomyocytes injury model was induced by PA. CCK-8 was conducted to assess the viability of cardiomyocytes, and the glucose uptake of cardiomyocytes was measured using glucose uptake test. Result: H&E staining revealed that the degree of hypertrophy and swelling of cardiomyocytes and cardiac fibrosis of miR208a-/- knockout mice in the high-fat diet group was significantly increased. Moreover, high levels of IRS-2, p-AKT, AKT, NPPA ,GLUT4, MYH7 and MYH6 expression in miR208a-/- knockout mice. Therefore, AKT, MYH6, IRS-2, NPPA in miR208a-/- knockout mice of high-fat diet. In PA-treated cardiomyocytes, the viability was markedly declined and glucose uptake was significantly reduced, while the lipid accumulation and fibrosis were significantly enhanced. Most importantly, the cardiomyocytes injury induced by PA was aggravated in miR-208a-3p upregulated cardiomyocytes, but alleviated in miR-208a-3pdownregulated cardiomyocytes. Conclusion: Our results indicate that the high expression of miR-208a promote the suppression of IRS-2/PI3K/AKT signaling pathway. Meanwhile, miR-208a-3p contributes to promoting PA-induced cardiomyocyte injury, which may be a biomarker of cardiomyocyte injury in lipotoxic cardiomyopathy." @default.
• W4313447962 created "2023-01-06" @default.
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• W4313447962 date "2022-12-20" @default.
• W4313447962 modified "2023-10-17" @default.
• W4313447962 title "Up-regulation of miR-208a aggravates high-fat -diet-induced cardiomyocytes injury by targeting IRS-2/PI3K/AKT pathway" @default.
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• W4313447962 doi "https://doi.org/10.21203/rs.3.rs-2375837/v1" @default.
• W4313447962 hasPublicationYear "2022" @default.
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