Modifying Reductive Stress Helps Personalize Treatment for Heart Failure

Personalized treatment for heart failure patients can be formulated by understanding how reductive stress is controlled as per a study at the University of Alabama at Birmingham, published in the journal Scientific Reports.

Oxidative stress has been linked to heart failure for a long time. Reductive stress is due to imbalance in the normal oxidation/reduction homeostasis that occurs as a result of pathological changes in heart failure.

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‘A microRNA network is found to be the putative molecular regulator of pathological chronic reductive stress in the heart. Understanding how this reductive stress is controlled may help personalize treatment for better outcomes among heart failure patients.’

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The progressive weakening of the heart muscle due to stress can also lead to death. Several attempts at antioxidant therapy have been proven ineffectual. The study team had earlier found that about one in six heart failure patients show reductive stress as per their clinical study in 2018.

The team now describes that a microRNA (miRNAs – short, non-coding RNAs that regulate gene expression) network is the putative molecular regulator of this pathological chronic reductive stress.

miRNAs and Oxidative Stress

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The miRNAs are known to be a fine-tuned controller of cell metabolism or the cell’s response to stress and adverse challenges, like oxidative stress in the heart. Nrf2 is a master transcriptional regulator that expresses genes for an antioxidant activity for heart muscle cells after a heart attack.

Studies also report that Nrf2 deficiency inhibits the expression of several miRNAs in the heart. However, persistent Nrf2 activation can paradoxically result in reductive stress.

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These relationships in the heart were analyzed by the study in the mouse model that overexpresses Nrf2 in cardiomyocytes to identify the miRNA network. It was found that a subset of miRNAs appeared to be a direct and dose-dependent target of Nrf2, and putative regulators of reductive stress.

These cells were named as “reducto-meers.” Since miRNAs are known to silence the gene expression at the post-transcriptional level, the team speculates that a distinct subset of genes could represent reductomiR targets for negative regulation.

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The study emphasizes the need for further mechanistic studies to confirm the functions of these mediators. The findings may further help personalize the treatment of heart failure patients for better outcomes.

Source-Medindia