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Arterioscler Thromb Vasc Biol. 2013 Jun;33(6):1392-400. doi: 10.1161/ATVBAHA.112.300741. Epub 2013 Apr 4.

Characterization of levels and cellular transfer of circulating lipoprotein-bound microRNAs.

Author information

1
Institute of Cardiovascular Regeneration, Centre for Molecular Medicine, Goethe-University Frankfurt, Frankfurt, Germany.

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 miRs are detected in HDL and to a lesser extent in low-density lipoprotein, and the miR-signatures are only slightly altered in patients with coronary artery disease. Lipoprotein-bound miRs were not efficiently delivered to endothelial, smooth muscle, and peripheral blood mononuclear cells suggesting that the lipoprotein-associated pool of miRs is not regulating the function of the studied cells in vitro.

KEYWORDS:

cardiovascular disease; circulation; endothelial cells; high-density lipoprotein; microRNA

PMID:
23559634
DOI:
10.1161/ATVBAHA.112.300741
[Indexed for MEDLINE]
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