Ischemia reperfusion (I/R) injury is an inevitable event arising during the cardiovascular diseases development and the process of potent surgical treatments. microRNAs (miRNAs) are critical regulators of multiple cell processes including I/R injury. A recent study published by researchers from The Second Affiliated Hospital of Anhui Medical University aimed to quantify miRNA alterations and regulated genes upon hypoxia-reoxygenation (H/R) injury in a rat heart failure model comparing with normal cardiomyocytes.

Chronic heart failure was established by injecting doxorubicin (2 mg/kg/week) for 6 weeks, then H/R was performed on primary cultured cardiomyocytes isolated from normal and failed heart. Cellular injury was evaluated by detecting LDH release levels, cell variability and apoptotic rate. Dysregulated miRNAs in control, hypoxia preconditioning (HPC) and morphine preconditioning (MPC) groups under two conditions were quantified by miRNA microarray analysis. Fas protein expression was analyzed using Western Blotting analysis.

Chronic heart failure was confirmed with lower ejection fraction (EF), and significant cellular injury. HPC could reverse the injury induced by H/R in normal heart rather than failed heart, otherwise, MPC significantly attenuated cellular injury dose dependently in both conditions. There was 12 miRNAs significantly altered after doxorubicin injection, 7 downregulated and 5 upregulated. miR-133b-5p, miR-6216, miR-664-1-5p and let7e-5p were differentially expressed after HPC and MPC treatments. The direct interaction between miR-133b-5p and target gene Fas were established. The Fas protein expression was manipulated by MPC not HPC affording protective effect against H/R injury.

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Reference
H-J Zhu, Z-Y Han, S-F He, S-Y Jin, S-J Xu, X-D Fang, Y. Zhang (2017) Specific MicroRNAs comparisons in hypoxia and morphine preconditioning against hypoxia-reoxgenation injury with and without heart failure Life Sci 170 pp 82-92  doi: 10.1016/j.lfs.2016.11.028 [abstract]

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