Human umbilical vein endothelial cell miRNA secretome highlights endothelial origin of serum miRNAs

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.