RBCs from pre-eclamptic women induce endothelial dysfunction

Red blood cells (RBCs) play a key role in facilitating the association between endothelial dysfunction and pre-eclampsia through arginase-dependent and oxidative stress-dependent mechanisms, according to a recent study. Thus, targeting of RBC arginase may provide a novel treatment modality of pre-eclampsia.

To determine if reduced nitric oxide (NO) bioavailability and increased reactive oxygen species (ROS) in pre-eclampsia was mediated via RBC-dependent mechanisms, the authors isolated plasma and RBCs from gestationally matched pre-eclamptic and healthy pregnant women and co-incubated these with mouse aortas for vascular reactivity studies. NO bioactivity was examined in plasma, while arginase activity and expression were analysed in RBCs.

Pre-eclamptic women had reduced plasma markers of NO homeostasis and signaling compared with healthy pregnant women. Co-incubation of aorta with pre-eclamptic RBCs caused endothelial dysfunction, which was improved by pharmacological inhibition of arginase, scavenging of ROS, and by nitrite treatment. This pathological vascular phenotype was not seen after incubation with pre-eclamptic plasma.

Furthermore, arginase expression and activity in RBCs were elevated in pre-eclamptic women compared with their healthy pregnant counterparts and was associated with pre-eclamptic severity. Of note, pre-eclamptic RBC-induced endothelial dysfunction was not due to the increased haemolysis/cell-free haemoglobin.

“Pre-eclampsia is a multisystem disorder associated with systemic vascular dysfunction and decreased NO bioactivity,” the authors said. “Arginase competes with NO synthase for l-arginine, and its upregulation may reduce NOS-derived NO formation or induce production of ROS via uncoupling of NOS, resulting in endothelial dysfunction.”