The pivotal role of miRNA-21 in myocardial metabolic flexibility in response to short- and long-term high glucose treatment: Evidence in human cardiomyocyte cell line

miRNA-21 在短期和长期高糖治疗后心肌代谢灵活性中的关键作用:人类心肌细胞系的证据

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作者:Lucia Scisciola, Rosaria Benedetti, Ugo Chianese, Rosaria Anna Fontanella, Nunzio Del Gaudio, Raffaele Marfella, Surina, Lucia Altucci, Michelangela Barbieri, Giuseppe Paolisso

Aim

miRNA-21 is a crucial regulator of developing cardiac diseases, but its role is still controversial, and therefore it is necessary to clarify, at cardiac level, its involvement in high glucose induced-acute and chronic cardiac damage.

Conclusion

In human cardiomyocytes, the abundance of miRNA-21 takes part in first defense mechanism against cardiac insult and its cardioprotective effect depends on time of exposure to injury. Moreover, miRNA-21 regulates mitochondrial respiration and the ability of cells to select the most appropriate substrate for ATP production in given environment.

Methods

Human ventricular cardiac myoblasts AC16, treated and not with miRNA-21 inhibitor, were exposed to high glucose for 2 and 7 days, and the expression of damage markers were investigated. Further, cardiac energetic metabolism was evaluated by measuring both the expression of glucose transporters and lipids regulators.

Results

Short-term high glucose treatment induced a significant increase in miRNA-21 expression (p < 0.05) that was associated with an increase in hydrogen ion flux and energy potential dissipation without any change in energy production or increase in genes expression involved in cellular damage. miRNA-21 reduction observed (p < 0.05) at 7 days of high glucose treatment, induced the activation of damage pathways and compromised mitochondrial function (p < 0.05).

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