Downregulation of Erythrocyte miR-210 Induces Endothelial Dysfunction in Type 2 Diabetes
| Autor: | John Pernow, Till Seime, Jiangning Yang, Ekaterina Chernogubova, Xiaowei Zheng, Sergiu-Bogdan Catrina, Ali Mahdi, Aida Collado, Yahor Tratsiakovich, Lars Maegdefessel, Ulf Hedin, Michael Alvarsson, Tong Jiao, Sampath Narayanan, Hong Jin, Changyan Sun, Hanna Winter, Zhichao Zhou |
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| Rok vydání: | 2021 |
| Předmět: |
Male
medicine.medical_specialty Erythrocytes endocrine system diseases Endocrinology Diabetes and Metabolism medicine.disease_cause Diabetes Mellitus Experimental Mice Downregulation and upregulation In vivo Internal medicine Internal Medicine Medicine Animals Humans Endothelial dysfunction Rats Wistar Cells Cultured Whole blood chemistry.chemical_classification Mice Knockout Protein Tyrosine Phosphatase Non-Receptor Type 1 Reactive oxygen species business.industry nutritional and metabolic diseases hemic and immune systems medicine.disease Rats MicroRNAs Endocrinology chemistry Diabetes Mellitus Type 2 Case-Control Studies Knockout mouse Endothelium Vascular business Reactive Oxygen Species Ex vivo Oxidative stress Diabetic Angiopathies circulatory and respiratory physiology |
| Popis: | Red 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. |
| Databáze: | OpenAIRE |
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