Abstract
Intercellular communication allows for molecular information to be transferred from cell to cell, in order to maintain tissue or organ homeostasis. Alteration in the process due to changes, either on the vehicle or the cargo information, may contribute to pathological events, such as cardiac pathological remodeling. Extracellular vesicles (EVs), namely exosomes, are double-layer vesicles secreted by cells to mediate intercellular communication, both locally and systemically. EVs can carry different types of cargo, including non-coding RNAs (ncRNAs), which, are major regulators of physiological and pathological processes. ncRNAs transported in EVs are functionally active and trigger a cascade of processes in the recipient cells. Upon cardiac injury, exosomal ncRNAs can derive from and target different cardiac cell types to initiate cellular and molecular remodeling events such as hypertrophic growth, cardiac fibrosis, endothelial dysfunction, and inflammation, all contributing to cardiac dysfunction and, eventually, heart failure. Exosomal ncRNAs are currently accepted as crucial players in the process of cardiac pathological remodeling and alterations in their presence profile in EVs may attenuate cardiac dysfunction, suggesting that exosomal ncRNAs are potential new therapeutic targets. Here, we review the current research on the role of ncRNAs in intercellular communication, in the context of cardiac pathological remodeling.
Highlights
Cardiac homeostasis is achieved through a complex network of interactions between the different cells of the myocardium, including cardiomyocytes, cardiac fibroblasts, neurons, cardiac endothelial, and immune cells
Cardiac communication between different types of cells can occur via (i) cell–matrix interactions, where cells respond to mechanical and extracellular matrix (ECM) stress; (ii) synaptic signaling, usually associated with electric and chemical neuronal signals released at the synapse site; (iii) endocrine signaling, a long distance communication where signaling factors are released into the blood stream (Kamo et al, 2015); but mostly (iv) via paracrine signaling, a short-range crosstalk mechanism where signals are diffused through the extracellular space before being incorporated in non-coding RNAs (ncRNAs) in Cardiac Intercellular Communication recipient cells and instigating a response (Bang et al, 2015)
While extracellular vesicles (EVs) is a generic term to describe a double-layer vesicle endogenously secreted by cells, their different origin, size and surface markers allow us to categorize them into three main groups: microvesicles, exosomes, and apoptotic bodies (Raposo and Stoorvogel, 2013)
Summary
Cardiac homeostasis is achieved through a complex network of interactions between the different cells of the myocardium, including cardiomyocytes, cardiac fibroblasts, neurons, cardiac endothelial, and immune cells. NcRNAs are a heterogenous class of RNAs, classified mostly according to their size: small (miRNAs) or long (lncRNAs); shape: linear or circular (circRNAs), and cell position: nucleolar (snoRNAs) or cytoplasmic (Santosh et al, 2015; Figure 1). CircRNAs are ncRNAs (exon- or intron-derived) where the 3 and 5 ends, usually free in a linear RNA, are linked together forming a continuous loop (Greene et al, 2017) These structurally different RNAs were associated with cardiovascular diseases and were shown to serve as EV cargo (Zhou and Yu, 2017; Huang S. et al, 2019). We review the current research on the role of ncRNAs in intercellular communication, in the context of cardiac pathological remodeling
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