Pathologic mechanobiological interactions between red blood cells and endothelial cells directly induce vasculopathy in iron deficiency anemia

The correlation between cardiovascular disease and iron deficiency anemia (IDA) is well documented but poorly understood. Using a multi-disciplinary approach, we explore the hypothesis that the biophysical alterations of red blood cells (RBCs) in IDA, such as variable degrees of microcytosis and decreased deform -ability may directly induce endothelial dysfunction via mechanobiological mecha-nisms. Using a combination of atomic force microscopy and microfluidics, we observed that subpopulations of IDA RBCs (idRBCs) are significantly stiffer and smaller than both healthy RBCs and the remaining idRBC population. Further-more, computational simulations demonstrated that the smaller and stiffer idRBC subpopulations marginate toward the vessel wall causing aberrant shear stresses. This leads to increased vascular inflammation as confirmed with perfu-sion of idRBCs into our ''endothelialized'' microfluidic systems. Overall, our multi-faceted approach demonstrates that the altered biophysical properties of idRBCs directly lead to vasculopathy, suggesting that the IDA and cardiovascular disease association extends beyond correlation and into causation.

Automated summary

This study investigates the relationship between cardiovascular disease and iron deficiency anemia (IDA). It shows that subpopulations of IDA red blood cells (idRBCs) have different physical properties compared to healthy red blood cells, leading to their accumulation in the vessel wall and causing inflammation.