Characterization of Levels and Cellular Transfer of Circulating Lipoprotein-Bound MicroRNAs

Abstract

Objective-MicroRNAs are important intracellular regulators of gene expression, but also circulate in the blood being protected by extracellular vesicles, proteins, or high-density lipoprotein (HDL). Here, we evaluate the regulation and potential function of HDL-and low-density lipoprotein-bound miRs isolated from healthy subjects and patients with coronary artery disease. Approach and Results-HDL-bound miRs with known effects in the cardiovascular system were analyzed in HDL isolated from healthy subjects (n=10), patients with stable coronary artery disease (n=10), and patients with an acute coronary syndrome (n=10). In HDL from healthy subjects, miR-223 was detected at concentrations >10 000 copies/µg HDL, and miR-126 and miR-92a at about 3000 copies/µg HDL. Concentrations of most miRs were substantially higher in HDL as compared with low-density lipoprotein. However, HDL-bound miR-223 contributed to only 8% of the total circulating miRs. The signatures of miRs varied only slightly in HDL derived from patients with coronary artery disease. We did not observe a significant uptake of HDL-bound miRs into endothelial cells, smooth muscle cells, or peripheral blood mononuclear cells. However, patient-derived HDL transiently reduced miR expression particularly when incubated with smooth muscle and peripheral blood mononuclear cells. Conclusions-Circulating

Evaluation of MicroRNAs miR-196a, miR-30a-5P, and miR-490 as Biomarkers of Disease Activity among Patients with FSGS

“…In general, cellular miRNAs can passively leak from damaged cells or can be actively secreted into the extracellular space or circulation via the microvesicle pathway (34,35) or within HDL protein complexes (36,37). The expressions and functions of miR-196a, miR-30a, and miR-490 miRNAs in their respective tissues also support a role for these miRNAs as potential biomarkers of FSGS disease activity.…”

Patients After Splenectomy: Old Risks and New Perspectives

“…Newer studies recommend exploring not just the circulating miRNAs, but also their carriers (80). Circulating miRNAs are present in blood in three different forms: associated with Argonaute complexes (81), connected to lipoproteins (82) and encapsulated in extracellular vesicles (EVs) (83). The most appealing form of blood circulating miRNAs, are those associated with EVs.…”

Extracellular RNA profiles with human age

“…miRNAs are resistant to nucleases due to their small size and the fact that in body fluids, they are likely protected in extracellular evesicles (EVs) or bound to protein or high‐density lipoprotein (HDL) binding partners (Brase, Wuttig, Kuner & Sultmann, 2010; Cortez et al., 2012; Reid, Kirschner & van Zandwijk, 2011; Wagner et al., 2013). This reservoir of miRNAs may transit to other cells and tissues where in some cases they influence gene regulation and may play a role in physiology and pathology (Hergenreider et al., 2012; Wei et al., 2017; Zhang et al., 2010, 2015).…”