Circadian MicroRNAs in Cardioprotection.
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TLDR
This review will focus on circadian microRNAs in the context of cardioprotection and will highlight new discoveries, which could lead to novel therapeutic concepts to treat myocardial ischemia.Abstract:
The most dramatic feature of life on Earth is our adaptation to the cycle of day and night. Throughout evolutionary time, almost all living organisms developed a molecular clock linked to the light-dark cycles of the sun. In present time, we know that this molecular clock is crucial to maintain metabolic and physiological homeostasis. Indeed, a dysregulated molecular clockwork is a major contributing factor to many metabolic diseases. In fact, the time of onset of acute myocardial infarction exhibits a circadian periodicity and recent studies have found that the light regulated circadian rhythm protein Period 2 (PER2) elicits endogenous cardioprotection from ischemia. Manipulating the molecular clockwork may prove beneficial during myocardial ischemia in humans. MicroRNAs are small non-coding RNA molecules capable of silencing messenger RNA (mRNA) targets. MicroRNA dysregulation has been linked to cancer development, cardiovascular and neurological diseases, lipid metabolism, and impaired immunity. Therefore, microRNAs are gaining interest as putative novel disease biomarkers and therapeutic targets. To identify circadian microRNA-based cardioprotective pathways, a recent study evaluated transcriptional changes of PER2 dependent microRNAs during myocardial ischemia. Out of 352 most abundantly expressed microRNAs, miR-21 was amongst the top PER2 dependent microRNAs and was shown to mediate PER2 elicited cardioprotection. Further analysis suggested circadian entrainment via intense light therapy to be a potential strategy to enhance miR-21 activity in humans. In this review, we will focus on circadian microRNAs in the context of cardioprotection and will highlight new discoveries, which could lead to novel therapeutic concepts to treat myocardial ischemia.read more
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miRNAs as biomarkers for early cancer detection and their application in the development of new diagnostic tools
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miRNA‑145 inhibits myocardial infarction‑induced apoptosis through autophagy via Akt3/mTOR signaling pathway in vitro and in vivo
TL;DR: It is demonstrated that miRNA-145 inhibits myocardial infarction-induced apoptosis via autophagy associated with the Akt3/mTOR signaling pathway in viv and in vitro.
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MicroRNA-21 mediates the protective effects of salidroside against hypoxia/reoxygenation-induced myocardial oxidative stress and inflammatory response.
TL;DR: Evidence is provided of the beneficial effects of salidroside against myocardial I/R injury by reducing myocardian oxidative stress and inflammation which are enhanced by increasing miR-21 expression.
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The Circadian PER2 Enhancer Nobiletin Reverses the Deleterious Effects of Midazolam in Myocardial Ischemia and Reperfusion Injury.
TL;DR: Findings highlight PER2 as a cardioprotective mechanism and suggest the PER2 enhancers nobiletin or tangeritin as a preventative therapy for myocardial IR-injury in the perioperative setting where midazolam pretreatment occurs frequently.
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