Key result
miR-223-3p mimic reduces radiation-induced cardiotoxicity in mice by activating AMPK via PDE4D regulation.
Why the study?
Radiation-induced heart disease is a serious radiotherapy complication lacking effective or reversible treatment strategies, prompting investigation into the role and mechanism of microRNA-223-3p.
Does miR-223-3p mimic improve apoptosis, oxidative damage, and cardiac dysfunction in mice with radiation-induced heart disease?
Does miR-223-3p mimic improve apoptosis, oxidative damage, and cardiac dysfunction in mice with radiation-induced heart disease?
p-value: p=<0.05
miR-223-3p mimic protects against radiation-induced heart disease in a mouse model by reducing oxidative stress and apoptosis via the PDE4D/AMPK pathway.
Objectives: Radiotherapy improves the survival rate of cancer patients, yet it also involves some inevitable complications. Radiation-induced heart disease (RIHD) is one of the most serious complications, especially the radiotherapy of thoracic tumors, which is characterized by cardiac oxidative stress disorder and programmed cell death. At present, there is no effective treatment strategy for RIHD; in addition, it cannot be reversed when it progresses. This study aims to explore the role and potential mechanism of microRNA-223-3p (miR-223-3p) in RIHD. Methods: Mice were injected with miR-223-3p mimic, inhibitor, or their respective controls in the tail vein and received a single dose of 20 Gy whole-heart irradiation (WHI) for 16 weeks after 3 days to construct a RIHD mouse model. To inhibit adenosine monophosphate activated protein kinase (AMPK) or phosphodiesterase 4D (PDE4D), compound C (CompC) and AAV9-shPDE4D were used. Results: WHI treatment significantly inhibited the expression of miR-223-3p in the hearts; furthermore, the levels of miR-223-3p decreased in a radiation time-dependent manner. miR-223-3p mimic significantly relieved, while miR-223-3p inhibitor aggravated apoptosis, oxidative damage, and cardiac dysfunction in RIHD mice. In addition, we found that miR-223-3p mimic improves WHI-induced myocardial injury by activating AMPK and that the inhibition of AMPK by CompC completely blocks these protective effects of miR-223-3p mimic. Further studies found that miR-223-3p lowers the protein levels of PDE4D and inhibiting PDE4D by AAV9-shPDE4D blocks the WHI-induced myocardial injury mediated by miR-223-3p inhibitor. Conclusion: miR-223-3p ameliorates WHI-induced RIHD through anti-oxidant and anti-programmed cell death mechanisms via activating AMPK by PDE4D regulation. miR-223-3p mimic exhibits potential value in the treatment of RIHD.
No takes yet. Share an insight, caveat, or question.
Zhang et al. (2022) studied Radiation-induced heart disease (RIHD). miR-223-3p mimic vs. AAV9-scramble (control) was evaluated on Cardiac injury and dysfunction (EF, FS, oxidative stress, apoptosis) (p=<0.05). miR-223-3p mimic ameliorated whole-heart irradiation-induced cardiac toxicity, oxidative stress, and programmed cell death in mice by activating AMPK via PDE4D regulation.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: