Non-Coding RNAs in Cell-to-Cell Communication: Exploiting Physiological Mechanisms as Therapeutic Targets in Cardiovascular Pathologies

Abstract

Cardiovascular disease, the leading cause of death worldwide, has been characterized at the molecular level by alterations in gene expression that contribute to the etiology of the disease. Such alterations have been shown to play a critical role in the development of atherosclerosis, cardiac remodeling, and age-related heart failure. Although much is now known about the cellular and molecular mechanisms in this context, the role of epigenetics in the onset of cardiovascular disease remains unclear. Epigenetics, a complex network of mechanisms that regulate gene expression independently of changes to the DNA sequence, has been highly implicated in the loss of homeostasis and the aberrant activation of a myriad of cellular pathways. More specifically, non-coding RNAs have been gaining much attention as epigenetic regulators of various pathologies. In this review, we will provide an overview of the ncRNAs involved in cell-to-cell communication in cardiovascular disease, namely atherosclerosis, cardiac remodeling, and cardiac ageing, and the potential use of epigenetic drugs as novel therapeutic targets.

Crosstalk between ubiquitin ligases and ncRNAs drives cardiovascular disease progression

“…Advanced studies have shown that therapeutic strategies based on specific ncRNA modulation are promising candidates to improve CVDs ( 28 , 125 , 126 ). NcRNAs are also considered to be key novel regulators of cardiovascular function and risk factors, potentially serving as small-molecule targets (e.g., miRNAs, lncRNAs, circRNAs and lincRNAs) or gene silencing tools (e.g., siRNAs) for cardiovascular treatment and prognosis assessment ( 23 , 28 ).…”

“…First, RNA molecules may evoke the host’s immune system and result in adverse immune responses. Second, because of the general nature of their targets, ncRNA-based drugs might not target specific sites ( 125 ). Therefore, current studies have proposed that ncRNAs combined with biocompatible nanoparticles (NPs) can offer better therapeutic properties.…”

“…Therefore, current studies have proposed that ncRNAs combined with biocompatible nanoparticles (NPs) can offer better therapeutic properties. Using NPs as delivery vectors can reduce drug toxicity, facilitate targeted drug release, and increase drug bioavailability, which provides an optimized therapeutic strategy for the cardiovascular field ( 125 , 128 – 130 ). In addition, with the production of proteasome inhibitors, the UPS offers a new therapeutic frontier.…”

Special Issue “The Role of Non-Coding RNAs Involved in Cardiovascular Diseases and Cellular Communication”

“…A plethora of studies demonstrated the importance of ncRNAs in the cardiovascular system and their involvement in cell-to-cell communication [ 8 , 22 ]. In fact, it is now well known that ncRNAs are considered important communication molecules due to their potential to modulate gene expression at intra- and extra-cellular levels, being secreted or transported to other cell types [ 19 , 23 , 24 , 25 , 26 , 27 ].…”

“…For instance, exosomes, the smallest kind of extracellular vesicles, are able to carry different cargos, including RNAs, proteins, and lipids, which can have an impact on the target cell biology by regulating a plethora of different functions [ 23 , 28 ]. Exosomes are secreted by all cells under physiological and pathological conditions and are released by all cells from the cardiovascular system [ 29 ].…”