(Open access funding provided by Semmelweis University)
MicroRNAs are key contributors to blood-based biomarker research, however their potential
is hindered by the "noise" of their abundance even in healthy blood. Using HUVEC cultures
and their conditioned media as a model for endothelium and blood, we were able to
detect 574 different microRNAs. 166 of these were exclusively secreted, 155 only intracellular
and 253 were found in both states suggesting a highly ordered role in endocrine and
paracrine communication. The identified microRNA signatures exhibited higher degrees
of variability based on culture conditions rather than genetic background of donors.
We found that the endothelial secreted microRNA signature correlates greatly with
those found in blood serum (ρ = 0.749 ± 0.044), more so, than leukocyte secretory
microRNAs (ρ = 0.531 ± 0.044). These results demonstrate that the endothelium actively
secretes microRNAs dominating the microRNA composition of the blood making the endothelial
secretory microRNA signatures ideal representation of background "noise" of healthy
serum samples. These microRNA signatures are readily adapted to environmental cues;
making the standardisation of culture conditions a key concern. Our results also demonstrate
that the microarray technology has great use in precision microRNA biomarker discovery
using simple models, which should be utilised for further mapping of cell-type specific
healthy signatures to further refine blood-based diagnostics.
