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• W2980369530 abstract "Objective: Remote ischemic pre-conditioning (RIPC) is highly cardioprotective in models of ischemia-reperfusion (IR) injury but has not been tested in genetically modified mice. This study was design to test whether RIPC rescues cardiomyopathy induced by knockdown of autophagy-related 5 protein (Atg5). Approach and Results: Atg5 knockdown was induced by feeding tamoxifen diet for two weeks in Atg5 flox/flox Cre +/- (KD) mice which were created by crossing Atg5 flox/flox and heterozygous cardiac-specific Cre recombinase transgenic (Cre +/- ) mice. Atg5 flox/flox Cre -/- mice served as controls (CONT). Cardiac function was evaluated by echocardiography 28 days after tamoxifen induction. Autophagy proteins were determined by Western blot analysis. RIPC was induced by four cycles of five minutes of hind limb ischemia with tourniquet followed by five minutes reperfusion. Tamoxifen feeding knocked down Atg5 to 32% (CONT 0.91 ± 0.09 vs KD 0.29 ± 0.01, p < 0.01, n = 7), leading to 96% decrease of autophagy activity indicated by LC3-II/LC3-I ratio (CONT 0.96 ± 0.07 vs 0.06 ± 0.03, p < 0.01, n = 7). This was associated with significant cardiac dysfunction (LV ejection fraction, CONT 59.78% ± 3.26 vs KD 47.13% ± 2.50, n = 8 and 10, p < 0.01) and increased heart weight to body weight ratio (CONT 0.50 ± 0.02 vs KD 0.57 ± 0.01, n = 8 and 10, p < 0.01). RIPC increased levels of Atg5 in Atg5 KD mice by 183% (Sham 1.00 ± 0.16 vs RIPC 1.83 ± 0.14, p < 0.01, n = 11 and 13), leading to 148% increase of autophagy activity (Sham 0.99 ± 0.13 vs RIPC 1.47 ± 0.18, p < 0.05, n = 6 and 7), and resulted in rescued cardiac function in terms of heart weight (CONT 0.50 ± 0.01 vs KD 0.53 ± 0.10, n = 11 and 13 ) and LV ejection fraction (CONT 55.64% ± 2.45 vs 52.48% ±1.61, n = 11 and 13). RIPC also suppressed mTOR phosphorylation by 62% compared with sham procedure in Atg5 KD mice (Sham 1.00 ± 0.18 vs RIPC 0.45 ± 0.08 p < 0.01 n = 11 and 13) which was increased by 650% in Atg5 KD compared with CONT mice (CONT 1.23 ± 0.14 vs KD 6.35 ± 0.09, p < 0.01, n = 7). Conclusion: We conclude that RIPC rescues Atg5 knockdown-induced cardiomyopathy. Our data adds to the emerging data suggesting benefits of RIPC beyond acute cardioprotection in IR injury." @default.
• W2980369530 created "2019-10-25" @default.
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• W2980369530 date "2019-08-02" @default.
• W2980369530 modified "2023-10-16" @default.
• W2980369530 title "Abstract 168: Remote Ischemic Preconditioning Rescues Cardiac Dysfunction in Atg5 Knockdown Mice" @default.
• W2980369530 doi "https://doi.org/10.1161/res.125.suppl_1.168" @default.
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