Exosomal miRNAs as potential biomarkers of cardiovascular risk in children

Abstract

Intercellular interactions are essential for basic cellular activities and errors in either receiving or transferring these signals have shown to cause pathological conditions. These signals are not only regulated by membrane surface molecules but also by soluble secreted proteins, thereby allowing for an exquisite coordination of cell functions. Exosomes are released by cells upon fusion of multivesicular bodies (MVB) with the plasma membrane. Their envelope reflects their cellular origin and their surface and internal contents include important signaling components. Exosomes contain a wide variety of proteins, lipids, RNAs, non-transcribed RNAs, miRNAs and small RNAs that are representative to their cellular origin and shuttle from donor cells to recipient cells. The exosome formation cargo content and delivery is of immense biological interest because exosomes are believed to play major roles in various pathological conditions, and therefore provide unique opportunities for biomarker discovery and development of non-invasive diagnostics when examined in biological fluids such as urine and blood plasma. For example, circulating miRNAs in exosomes have been applied as functional biomarkers for diagnosis and outcomes prediction, while synthetic miRNAs in polymer-based nanoparticles are applicable for therapeutics. This review provides insights into the composition and functional properties of exosomes, and focuses on their potential value as diagnostic markers in the context of cardiovascular disease risk estimates in children who suffer from conditions associated with heightened prevalence of adverse cardiovascular disease, namely obesity and sleep-disordered-breathing.

Circulating Plasma Extracellular Microvesicle MicroRNA Cargo and Endothelial Dysfunction in Children with Obstructive Sleep Apnea

“…Based on the selectivity of miRNA loading into extracellular vesicles (EV) and their stability (45), potential differences in miRNA exosomal cargo were identified, and were compatible with previous work implicating exosomal miRNAs not only in angiogenesis and other vascular phenomena (46,47), while also suggesting the possibility that exosomes may provide therapeutic opportunities (48). We recently assessed the biomarker capabilities of plasma miRNAs (19), and our findings support the driving assumption that a cluster of circulating miRNAs may reliably discern between children with ED and children with NEF. Among, the five differentially miRNAs identified through microarray approaches, a search of the literature revealed scarce information about these miRNAs regarding possible vascular targets (49).…”

“…Exosomes are 30-to 100-nm vesicular structures that contain a wide variety of proteins, lipids, RNAs, nontranscribed RNAs, microRNAs (miRNAs), and small RNAs. These diverse cargos allow exosomes to provide unique opportunities for biomarker discovery and development of noninvasive diagnostics when examined in biologic fluids, such as urine and blood plasma, and formulation of novel therapies (5,11,13,(15)(16)(17)(18)(19)(20)(21).…”

Treatment outcomes of obstructive sleep apnoea in obese community-dwelling children: the NANOS study

“…These findings also indicate the need to develop effective tools that will enable objective and accurate prediction of the response to treatment of obese children with OSAS [41][42][43][44][45], and the identification of those at risk for developing OSAS with end-organ damage.…”

Circulating microRNAs as Potential Biomarkers of Endothelial Dysfunction in Obese Children

“…16 Circulating miRNAs are protected from RNase-dependent degradation by several mechanisms, including their inclusion in microvesicles, exosomes, and apoptotic bodies as well as through formation of protein-miRNA complexes that are resistant to degradation. 17 Of note, although the expression of miRNAs in plasma and serum are believed to reflect the extrusion of miRNAs from relevant remote tissues or organs or disease processes, 18 it is likely that peripheral blood miRNAs do not reflect miRNAs expressed in remote tissues. miRNAs are involved in the regulation of several key cellular processes, including cellular development, differentiation, proliferation, cell death, and metabolism.…”