The Role of ncRNAs in Cardiac Infarction and Regeneration

Abstract

Myocardial infarction is the most prevalent cardiovascular disease worldwide, and it is defined as cardiomyocyte cell death due to a lack of oxygen supply. Such a temporary absence of oxygen supply, or ischemia, leads to extensive cardiomyocyte cell death in the affected myocardium. Notably, reactive oxygen species are generated during the reperfusion process, driving a novel wave of cell death. Consequently, the inflammatory process starts, followed by fibrotic scar formation. Limiting inflammation and resolving the fibrotic scar are essential biological processes with respect to providing a favorable environment for cardiac regeneration that is only achieved in a limited number of species. Distinct inductive signals and transcriptional regulatory factors are key components that modulate cardiac injury and regeneration. Over the last decade, the impact of non-coding RNAs has begun to be addressed in many cellular and pathological processes including myocardial infarction and regeneration. Herein, we provide a state-of-the-art review of the current functional role of diverse non-coding RNAs, particularly microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), in different biological processes involved in cardiac injury as well as in distinct experimental models of cardiac regeneration.

Propofol synergizes with circAPBB2 to protect against hypoxia/reoxygenation‐induced oxidative stress, inflammation, and apoptosis of human cardiomyocytes

“…Dill et al have reported that the imprinted Dlk1‐Dio3 genomic region that contains a noncoding RNA cluster and regulates cardiac homeostasis has the potential as a therapeutic target for CVDs 23 . Convincing evidence has indicated the contribution of circRNAs to cardiac inflammation, cardiac fibrosis, cardiac regeneration, autophagy, apoptosis, and oxidative stress signaling during myocardial infarction 24 . The present work was the first one to report the role of circAPBB2 in human myocardial I/R injury.…”

“…23 Convincing evidence has indicated the contribution of circRNAs to cardiac inflammation, cardiac fibrosis, cardiac regeneration, autophagy, apoptosis, and oxidative stress signaling during myocardial infarction. 24 The present work was the first one to report the role of circAPBB2 in human myocardial I/R injury. We found that PPF treatment synergized with circAPBB2 to protect against hypoxia-induced cell injury through regulation of the miR-18a-5p/DUSP14 pathway.…”

Sirtuin 1-activating derivatives belonging to the anilinopyridine class displaying in vivo cardioprotective activities

“…Resveratrol is often considered as the lead compound for SIRT1-activators and numerous papers confirm its anti-ischemic cardioprotection. [25][26][27][28][29] However, the clinical use of this polyphenol is limited by its disadvantageous pharmacokinetic profile. Therefore, great efforts are currently being focused on the obtainment of novel agents able to stimulate SIRT1 enzyme with a more favorable bioavailability than that of resveratrol.…”

Exploring the Multifaceted Biologically Relevant Roles of circRNAs: From Regulation, Translation to Biomarkers

“…Despite the challenges involved in definitively proving the sponging of miRNA through individual circRNAs [12], the advancement of online bioinformatic tools to assess potential binding sites for circRNA-miRNA interaction, such as Circ Interactome, CircNet, Circ2Traits, and StarBase [29], along with an experimental investigation through RT-qPCR using divergent primers [82], dual-luciferase reporter assays [83], Argonaute (Ago) immunoprecipitation [84], fluorescent in situ Hybridization (FISH) assays [85], and silencing and overexpressing target circRNAs [86], has enabled the discovery of numerous circRNA-miRNA interactions over the past decade. This well-documented function of circRNAs has also garnered recent appreciation in the context of cardiovascular biology and diseases [59,87]. Figure 3 summarizes different scenarios reported regarding the role of circRNAs as miRNA sponges within the contexts of disease, cellular and developmental biology.…”