文章基本信息

标题：Pathologic mechanobiological interactions between red blood cells and endothelial cells directly induce vasculopathy in iron deficiency anemia
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作者：Christina Caruso ; Meredith E. Fay ; Xiaopo Cheng 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2022
卷号：25
期号：7
页码：1-17
DOI：10.1016/j.isci.2022.104606
语种：English
出版社：Elsevier
摘要：SummaryThe 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 deformability may directly induce endothelial dysfunction via mechanobiological mechanisms. 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. Furthermore, 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 perfusion of idRBCs into our “endothelialized” microfluidic systems. Overall, our multifaceted 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.Graphical abstractDisplay OmittedHighlights•Subpopulations of stiff and small red blood cells (RBCs) exist in iron deficiency anemia (IDA)•Small and stiff cells marginate toward vessel walls, causing aberrant shear stress•Increased cell margination leads to increased vascular inflammationin vitro•Altered biophysical properties of iron-deficient RBCs induce vasculopathyMechanobiology; Disease; Biological sciences; Human Physiology; Cell biology; Biophysics