查看更多>>摘要：Abstract Myocardial infarction (MI) causes most of the mortality worldwide. Coronary obstruction–caused myocardial ischemic injury leads to permanent loss of the myocardium. Subsequent compensatory myocardial remodeling and heart failure would result in arrhythmia and even sudden death. The molecular mechanisms of these pathological processes remain to be thoroughly revealed. Circular RNAs (circRNAs) are special types of non-coding RNAs which can durably regulate gene expression and modulate cell fate. They had been reported to mediate ischemic myocardial injury and myocardial remodeling. circRNAs can be loaded into extracellular vesicles and released into extracellular space. More recently, it was uncovered that the extracellular circRNAs can regulate intercellular communications, similar to “first messengers.” The cross-talk mediated by extracellular circRNAs had been demonstrated to play important roles in pathological processes. Here, we would like to review the modulation of extracellular circRNAs in ischemic myocardial injury and myocardial remodeling. We believe the extracellular circRNAs can bring new strategies of MI treatment.
查看更多>>摘要：Abstract Extracellular vesicles (EVs), including exosomes and microvesicles, emerge to be crucial mediators of cell-to-cell communication in multiple organs. Non-coding RNAs loaded inside EVs contribute as one major mechanism for remote information transfer among different cell types or organs. Increasing evidence suggests that EV-associated non-coding RNAs derived from cardiovascular or non-cardiac cells regulate cardiovascular pathophysiology in heart development and diseases. The functional relevance of the EV-associated ncRNAs in heart diseases provides an avenue to develop novel diagnostic tools and therapies for heart diseases. In this review, we summarize the recent advancement of EV-associated ncRNAs in different cardiovascular diseases, including myocardial infarction, arrhythmias, cardiac hypertrophy, and heart failure, with an emphasis on the underlying molecular mechanisms.
查看更多>>摘要：Abstract Diabetic cardiomyopathy (DCM) is one of the major causes of heart failure in diabetic patients. However, the pathogenesis of diabetic cardiomyopathy has not been fully elucidated. Diagnosis and therapeutic strategy of DCM is still challenging. Various non-coding RNAs (ncRNA) are implicated in the onset and progression of DCM. Interestingly, ncRNAs not only are regulators intracellularly, but also can exist and function in extracellular space. Recent evidences have demonstrated that extracellular ncRNAs play emerging roles in both intracardiac and inter-organ communication during the pathogenesis of DCM; thus, extracellular ncRNAs are attractive diagnostic biomarkers and potential therapeutic targets for DCM. This article will review the current knowledge of the roles of extracellular ncRNAs in DCM, especially focusing on their physio-pathological properties and perspectives of potential clinical translation for biomarkers and therapies.Graphical abstract Recent evidences have demonstrated that extracellular ncRNA play emerging roles in both intracardiac and inter-organ communication involved in the pathogenesis of diabetic cardiomyopathy (DCM), thus shown as attractive diagnostic biomarkers and potential therapeutics for DCM. In the current review, we first summarize the progress regarding the paracrine role of extracellular ncRNA in DCM. miRNAs and circRNAs have been shown to mediate the communication among cardiomyocytes, endothelial cells, and vascular smooth muscle cells in the diabetic heart. Subsequently, we systematically describe that extracellular ncRNAs contribute to the crosstalk between the heart and other organs in the context of diabetes. Researches have indicated that miRNAs acted as hepatokines and adipokines to mediates the injure effect of distal organs on hearts. As for clinical application, extracellular ncRNAs are promising biomarker and have therapeutic potential. (Created with BioRender.com)
查看更多>>摘要：Abstract Atherosclerosis (AS) is a complex chronic inflammatory disease that leads to myocardial infarction, stroke, and disabling peripheral artery disease. Non-coding RNAs (ncRNAs) directly participate in various physiological processes and exhibit a wide range of biological functions. The present review discusses how different ncRNAs participate in the process of AS in various carrier forms. We focused on the role and potential mechanisms of extracellular ncRNAs in AS and examined their potential implications for clinical treatment.
查看更多>>摘要：Abstract Extracellular vesicles (EVs) are secreted by cells and carry diverse components, including proteins, lipids, nucleic acids, and metabolites. EVs could be found in blood and other biofluids. They vary greatly in size, function, cargo, and cellular origin. Accumulating evidence shows that extracellular non-coding RNAs, the dominant extracellular RNAs encapsulated into EVs, function as critical mediators of cell–cell communication and play critical roles in human health and disease. Blood vessels form a dense network that nourishes all of the body’s tissues. These vascular networks’ dysregulated functions contribute to vascular diseases, such as pulmonary arterial hypertension (PAH), hypertension, atherosclerosis, and aneurysm. With the increase in unhealthy lifestyle-associated obesity and metabolic disorders, vascular diseases are becoming serious medical and public health issues with a profound global economic burden. The present review summarizes the latest advances on extracellular non-coding RNAs in pathological vascular remodeling-associated diseases, briefly describing vessel-associated extracellular non-coding RNAs and their mechanisms of action.
查看更多>>摘要：Abstract Sympathetic hyperactivity plays an important role in the progression of chronic heart failure (CHF). It is reported that inflammation in the rostral ventrolateral medulla (RVLM), a key region for sympathetic control, excites the activity of neurons and leads to an increase in sympathetic outflow. Exosome, as the carrier of microRNAs (miRNAs), has the function of crossing the blood–brain barrier. The present study was designed to investigate the effect of exosomal miRNAs on central inflammation via peripheral-central interaction in CHF. The miRNA microarray detection was performed to compare the difference between circulating exosomes and the RVLM in CHF rats. It was shown that the expression of miR-214-3p was significantly up-regulated, whereas let-7g-5p and let-7i-5p were significantly down-regulated in circulating exosomes and the RVLM. Further studies in PC12 cells revealed that miR-214-3p enhanced the inflammatory response, while let-7g-5p and let-7i-5p reduced the neuroinflammation. The direct interaction between the miRNA and its inflammatory target gene (miR-214-3p, Traf3; let-7g-5p, Smad2; and let-7i-5p, Mapk6) was confirmed by the dual-luciferase reporter assay. These results suggest that the circulating exosomes participate in the enhancement of inflammatory response in the RVLM through their packaged miRNAs, which may further contribute to sympathetic hyperactivity in CHF.
查看更多>>摘要：Abstract Stem cell-based therapy for ischemic heart disease (IHD) has become a promising but controversial strategy during the past two decades. The fate and effects of stem cells engrafted into ischemia myocardium are still not fully understood. Stem cell-derived exosomes, a subcategory of extracellular vesicles with nano size, have been considered as an efficient and safe transporter for microRNAs (miRNAs) and a central mediator of the cardioprotective potentials of the parental cells. Hypoxia, pharmacological intervention, and gene manipulation could alter the exosomal miRNAs cargos from stem cells and promote therapeutic potential. Furthermore, several bioengineering methods were also successfully applied to modify miRNAs content and components of exosomal membrane proteins recently. In this review, we outline relevant results about exosomal miRNAs from stem cells and focus on the current strategies to promote their therapeutic efficiency in IHD.
查看更多>>摘要：Abstract Ischemic diseases are life-threatening, and the incidence increases as people’s lifestyles change. Medications and surgical intervention offer limited benefit, and stem cell therapy has emerged as a potential approach for treating ischemic diseases. The exosomes secreted by stem cells have attracted more attention because they do not trigger the immune response and can be used as drug carriers. The non-coding RNA (ncRNA) carried by exosomes plays a key role in mediating exosome’s beneficial effect, which can be further enhanced when combined with nanomaterials to improve its retention time. Here, we review the downstream target molecules and signal pathways of ncRNA and summarize recent advances of some nanomaterials used to encapsulate exosomes and promote ischemic tissue repair. We highlight the imprinting of exosomes from parent cells and discuss how the inflammasome pathway may be targeted for the development of novel therapy for ischemic diseases.
查看更多>>摘要：Abstract? Hypertension is the leading risk factor for cardiovascular disorders. This study aimed to explore roles of microRNA (miR)-122-5p in hypertension. Angiotensin II (Ang II; 1.5?mg/kg/day) with an osmotic minipump was used to induce hypertensive rats pretreated by rAAV-miR-122-5p or rAAV-GFP, respectively. Notably, Ang II infusion caused marked increases in myocardial fibrosis, inflammation, oncosis, and oxidant injury in rats, which were aggravated by rAAV-miR-122-5p. RAAV-miR-122-5p exacerbated Ang II–mediated cardiac dysfunction and structural injury in hypertensive rats, with downregulated levels of apelin, elabela, ACE2, and GDF15, as well as upregulated expression of?porimin and CTGF. In cultured rat cardiac fibroblasts, Ang II contributed to augmentation of cellular oncosis, migration, inflammation, and oxidative stress, with reduction of apelin, elabela, ACE2, and GDF15?levels, which were rescued by miR-122 inhibitor. In summary, miR-122-5p exacerbates myocardial fibrosis and dysfunction in hypertensive rats by modulating the elabela/apelin-ACE2-GDF15 signaling. MiR-122-5p has potential therapeutic significance for?hypertension and hypertensive cardiac injury.Graphical abstract
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