Circadian MicroRNAs in Cardioprotection

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 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.

miR‑21/PTEN pathway mediates the cardioprotection of geniposide against oxidized low‑density�lipoprotein‑induced endothelial injury via suppressing oxidative stress and inflammatory response

“…miR-21, a highly expressed miRNA in the heart, has a crucial function of modulating normal biological processes of the myocardial tissue (40). Accumulating evidence also suggests that the miR-21/PTEN pathway exhibits critical actions on cell survival and death in the cardiovascular system (24,41,42).…”

miRNA‑145 inhibits myocardial infarction‑induced apoptosis through autophagy via Akt3/mTOR signaling pathway in�vitro and in�vivo

“…Therefore, it exhibits the potential to act as a useful therapeutic target. Numerous studies have been conducted researching the pathogenesis of CVD ( 18 ). Furthermore, miRNA alterations have been demonstrated to be involved in angiogenesis, myocardial hypertrophy, heart failure and myocardial fibrosis ( 18 ).…”

“…Numerous studies have been conducted researching the pathogenesis of CVD ( 18 ). Furthermore, miRNA alterations have been demonstrated to be involved in angiogenesis, myocardial hypertrophy, heart failure and myocardial fibrosis ( 18 ). The present study demonstrated that the downregulation of miRNA-145 increased cardiac cell apoptosis in an in vitr model of AMI.…”

MicroRNA‑21 mediates the protective effects of salidroside against hypoxia/reoxygenation‑induced myocardial oxidative stress and inflammatory response

“…miR-21 expression is endogenously high in cardiomyocytes, vascular endothelial cells, cardiac fibroblasts and vascular smooth muscle cells (17). Although, the physiological functions of miR-21 in cardiovascular diseases have not been fully determined, the contribution of miR-21 in various cardiovascular diseases, including heart failure, myocardial infarction, myocardial fibrosis and atherosclerosis are being uncovered (18)(19)(20). Studies have shown that miR-21 is involved in numerous pathophysiological processes associated with myocardial I/R injury (21)(22)(23).…”