microRNA-25 as a treatment in heart failure
Ann Marie Karam
Introduction: Heart Failure (HF) contributes to 1 in 8 deaths in America, with a risk of 1 in 5 of developing HF in one’s lifetime. In addition, HF can be difficult to diagnose, especially since most patients who develop HF have multiple comorbidities and present with varying symptoms.1 Current treatments for heart failure (HF) are focused on diuretics that reduce the load on the heart and do not significantly reduce morbidity and/or mortality in patients.2,3 A change in direction for the treatment of HF is warranted, leading to research into microRNAs (miRs). miRs regulate and fine-tune nearly all normal and pathological processes by downregulating proteins at key points in biological networks. By targeting miRs that are dysregulated during HF, novel therapeutic targets can be found.4,5 Methods: Research articles looking at the effects of miRs, specifically miR-25, on HF within the past 5 years were found searching key words in PubMed. The absence, increase, and decrease of miR-25 was analyzed for its effects on specific molecules of the body and how these affected HF specifically.6,7,8 Results: miR-25 affects multiple pathways in the progression to HF. miR-25 is decreased in cholesterol-fed rat hearts and miRNA-25 is an important regulator of NADPH oxidase 4 (NOX4) expression and thereby cardiac oxidative/nitrative stress, a known contributor of myocardial dysfunction induced by hypercholesterolemia.8 Inhibition of miR-25 evokes cardiac dysfunction in a Heart- and neural crest derivatives-expressed protein 2 (Hand2)-dependent manner.6 miR-25 is a critical repressor of sarcoplasmic/endoplasmic reticulum Ca2+-ATPase (SERCA2a) and cardiac function during HF.7 Conclusions: miR-25 is an important factor in myocardial dysfunction and therefore HF due to hypercholesterolemia. Injection of miR-25 may help to reverse the underlying cause of HF and cardiac dysfunction. In contrast, injection of anti-miR-25, which would inhibit miR-25 in the body, would enhance cardiac contractility via de-repressing SERCA2a and could possibly be used as a treatment for HF. While miR-25 could potentially be a more effective therapy to help re-structure HF patients’ hearts, more research is needed for miR-25 and its interactions with each part of the heart before it can be used to either help prevent HF or to treat it.
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- Dirkx E, Gladka MM, Philippen LE, et al. Nfat and miR-25 cooperate to reactivate the transcription factor Hand2 in heart failure. Nature Cell Biology. 2013;15(11):1282–1293.
- Wahlquist C, Jeong D, Rojas-Muñoz A, et al. Inhibition of miR-25 Improves Cardiac Contractility in the Failing Heart. Nature. 2014;508(7497):531-535.
- Varga, Zoltan V, et al. MicroRNA-25-dependent up-regulation of NADPH oxidase 4 (NOX4) mediates hypercholesterolemia-induced oxidative/nitrative stress and subsequent dysfunction in the heart. Journal of Molecular and Cellular Cardiology. 2013;62:111-121.