Multiple Ways of cfDNA Reception and Following ROS Production in Endothelial Cells

Oxidized cell-free DNA acts as a stress signal molecule and triggers an adaptive response in human cells. Various membrane DNA recognizing receptors are known as potential sensors for such DNA fragments. In order to clarify which of these sensors are able to interact with cfDNA fragments, circulating in human blood flow in heath and disease, we studied the influence of various cfDNA types on endothelial cells. We incubated these fragments at a physiologically optimal concentration with HUVEC cells for 3-24 h and detected the expression of either TLR9 or AIM2, RIG1 and STING receptors at mRNA and protein levels. We estimated that the activation of both TLR9 and other types of intracellular receptors initiates stress signaling in the endothelium independently. Signal transduction through these receptors activates NOX4 as the main source of ROS production in HUVECs.