Exosomes and exosomal miRNAs in cardiovascular protection and repair

Abstract

Cell-cell communication between cardiac and vascular cells and from stem and progenitor cells to differentiated cardiovascular cells is both an important and complex process, achieved through a diversity of mechanisms that have an impact on cardiovascular biology, disease and therapeutics. In recent years, evidence has accumulated suggesting that extracellular vesicles (EVs) are a new system of intercellular communication. EVs of different sizes are produced via different biogenesis pathways and have been shown to be released and taken up by most of known cell types, including heart and vascular cells, and stem and progenitor cells. This review will focus on exosomes, the smallest EVs (up to 100 nm in diameter) identified so far. Cells can package cargoes consisting of selective lipids, proteins and RNA in exosomes and such cargoes can be shipped to recipient cells, inducing expressional and functional changes. This review focuses on exosomes and microRNAs in the context of cardiovascular disease and repair. We will describe exosome biogenesis and cargo formation and discuss the available information on in vitro and in vivo exosomes-based cell-to-cell communication relevant to cardiovascular science. The methods used in exosome research will be also described. Finally, we will address the promise of exosomes as clinical biomarkers and their impact as a biomedical tool in stem cell-based cardiovascular therapeutics.

Circulating microRNAs and hypertension—from new insights into blood pressure regulation to biomarkers of cardiovascular risk

“…It is also noteworthy that miR-92a was found to be present (and differentially expressed) in exosomes (isolated from serum), [13] which have been postulated to play a key role in facilitating microRNA-mediated cell-to-cell communication. [14,15] Pertinently, miR-92a was predicted to target AGTR1, the gene encoding the angiotensin II type I receptor (AT1R) -a key component of the renin-angiotensin system. Unfortunately, no in vitro validation was performed.…”

“…Whilst initially postulated simply to be reflective of disease states in tissues, there is mounting evidence that microRNAs may play a key role in cell-to-cell communication. [14,15] In hypertension, unbiased screens have identified a large number of microRNAs that appear dysregulated in hypertension, but these frequently vary between studies and lack validation -indeed, only a few microRNAs have been replicated across multiple studies (see Figure 1). There are many reasons why this may be the case: firstly, it could well be a reflection of the highly complex nature of hypertension and its multifactorial aetiology; secondly, and similarly, it could result from the wide-ranging clinical manifestations of persistent hypertension in multiple organs; thirdly, and perhaps more simply, these differences may be explained by inter-study variation of populations and methodologies or by the frequently small sample sizes employed.…”

TNF-Related Apoptosis-Inducing Ligand (TRAIL)–Armed Exosomes Deliver Proapoptotic Signals to Tumor Site

“…Selective protein delivery or gene therapy approaches through exosomes are already ongoing in neurodegenerative and cardiovascular diseases, with quite exciting preclinical results (24,25). One of the first clinical trials based on exosome administration was performed again in cancer several years ago, with exosomes produced by dendritic cells (Dexosomes), exploited to shuttle antigenic determinants of immune response, and to immunize patients in the context of cancer vaccines (26)(27)(28).…”

Mesenchymal Stem Cells Derived Extracellular Vesicles

“…Interestingly, bone marrow-derived MSCs (BM-MSCs) and adiposederived MSCs (ASCs) share similar representatives of RNAs despite differences in the relative proportions [7] . Micro RNA (miRNA) is a single strand of RNA with about 22 nucleotide length, single miRNA could repress several genes [13] . Both non coding RNA and miRNAs of EVs control gene expression post-transcriptionally, so they are related to cell survival and differentiation as well as regulation of the immune system [7] .…”