Assessment of Red Blood Cell Aggregation in Preeclampsia by Microfluidic Image Flow Analysis—Impact of Oxidative Stress on Disease Severity

Abstract

Preeclampsia (PE) is a hypertensive disease characterized by proteinuria, endothelial dysfunction, and placental hypoxia. Reduced placental blood flow causes changes in red blood cell (RBC) rheological characteristics. Herein, we used microfluidics techniques and new image flow analysis to evaluate RBC aggregation in preeclamptic and normotensive pregnant women. The results demonstrate that RBC aggregation depends on the disease severity and was higher in patients with preterm birth and low birth weight. The RBC aggregation indices (EAI) at low shear rates were higher for non-severe (0.107 ± 0.01) and severe PE (0.149 ± 0.05) versus controls (0.085 ± 0.01; p < 0.05). The significantly more undispersed RBC aggregates were found at high shear rates for non-severe (18.1 ± 5.5) and severe PE (25.7 ± 5.8) versus controls (14.4 ± 4.1; p < 0.05). The model experiment with in-vitro-induced oxidative stress in RBCs demonstrated that the elevated aggregation in PE RBCs can be partially due to the effect of oxidation. The results revealed that RBCs from PE patients become significantly more adhesive, forming large, branched aggregates at a low shear rate. Significantly more undispersed RBC aggregates at high shear rates indicate the formation of stable RBC clusters, drastically more pronounced in patients with severe PE. Our findings demonstrate that altered RBC aggregation contributes to preeclampsia severity.

The Role of Ergothioneine in Red Blood Cell Biology: A Review and Perspective

“…If these cytokines similarly affected bone marrow erythropoiesis by increasing SLC22A4 expression and function, then elevated circulating RBC ESH levels could provide a marker of disease activity. Similarly, in pre-eclampsia [ 115 ], the pathogenesis of which may also involve oxidative stress [ 116 ], this proposed mechanism could also explain the presence of elevated RBC ESH levels, perhaps as part of a compensatory process [ 117 ]. Finally, it is important to consider the possibility that elevated ESH levels in various tissues, including RBCs, may exacerbate cancer and certain infections by ameliorating the oxidative stress with which the host could target the pathogenic process [ 8 ].…”