Circ-Ddx60 contributes to the antihypertrophic memory of exercise hypertrophic preconditioning

Working model of this study. EHP significantly upregulates circular RNA Ddx60 (c-Ddx) in mouse myocardial tissue. c-Ddx exerts its function by binding eEF2. After binding eEF2, c-Ddx promotes phosphorylation of eEF2 and its upstream AMPK, generating a positive feedback pathway. Phosphorylation of eEF2 prevents protein translational elongation in pathological myocardial hypertrophy, and eventually produces an antihypertrophic effect, while activation of AMPK by c-Ddx/eEF2 complexus would also produce an antihypertrophic role through the well-known signal pathways. Abbreviations: EHP: exercise hypertrophic preconditioning; c-Ddx, circ-Ddx60; eEF2: eukaryotic elongation factor 2; AMPK: AMP-activated protein kinase; mTORC1, mammalian target of rapamycin kinase complex 1. ↑, activation; ⊥, inhibition; ---, pathway confirmed by previous studies. This picture was created with BioRender.com.