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Download fileDownregulation of Erythrocyte miR-210 Induces Endothelial Dysfunction in Type 2 Diabetes
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posted on 2021-11-09, 04:06 authored by Zhichao Zhou, Aida Collado, Changyan Sun, Yahor Tratsiakovich, Ali Mahdi, Hanna Winter, Ekaterina Chernogubova, Till Seime, Sampath Narayanan, Tong Jiao, Hong Jin, Michael Alvarsson, Xiaowei Zheng, Jiangning Yang, Ulf Hedin, Sergiu-Bogdan Catrina, Lars Maegdefessel, John PernowRed blood cells (RBCs) act as mediators of vascular
injury in type 2 diabetes mellitus (T2DM). miR-210 plays a protective role in
cardiovascular homeostasis and is decreased in whole blood of T2DM mice. We hypothesized that downregulation of RBC miR-210 induces endothelial
dysfunction in T2DM. RBCs were co-incubated with arteries and endothelial
cells ex vivo and transfused in vivo to identify the role of miR-210
and its target protein tyrosine phosphatase 1B (PTP1B) in endothelial dysfunction. RBCs from patients
with T2DM (T2DM RBC) and diabetic rodents induced endothelial dysfunction ex vivo and in vivo. miR-210 levels were lower in human T2DM RBC than in RBCs
from healthy subjects (H RBC). Transfection of miR-210 in human T2DM RBC rescued
endothelial function, whereas miR-210 inhibition in H RBC or RBCs from miR-210
knockout mice impaired endothelial function. Human T2DM RBC decreased miR-210 expression
in endothelial cells. miR-210 expression in carotid artery plaques was lower in
T2DM patients than in non-diabetic patients. Endothelial dysfunction induced by
downregulated RBC miR-210 involved PTP1B and reactive oxygen species. miR-210
mimic attenuated endothelial dysfunction induced by RBCs via downregulating
vascular PTP1B and oxidative stress in diabetic mice in vivo. These data reveal that the downregulation of RBC miR-210 is a novel mechanism driving the development of endothelial dysfunction in
T2DM.