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

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.

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).

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.