scholarly journals Serum‐Derived Small Extracellular Vesicles From Diabetic Mice Impair Angiogenic Property of Microvascular Endothelial Cells: Role of EZH2

2021 ◽  
Author(s):  
Zhongjian Cheng ◽  
Venkata Naga Srikanth Garikipati ◽  
May M. Truongcao ◽  
Maria Cimini ◽  
Grace Huang ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Extracellular Vesicles ◽  
Hind Limb ◽  
Blood Perfusion ◽  
Angiogenic Factors ◽  
Epigenetic Mechanism ◽  
Enhanced Expression ◽  
Microvascular Endothelial ◽  
Angiogenic Genes

Background Impaired angiogenic abilities of the microvascular endothelial cell (MVEC) play a crucial role in diabetes mellitus–impaired ischemic tissue repair. However, the underlying mechanisms of diabetes mellitus–impaired MVEC function remain unclear. We studied the role of serum‐derived small extracellular vesicles (ssEVs) in diabetes mellitus–impaired MVEC function. Methods and Results ssEVs were isolated from 8‐week‐old male db/db and db/+ mice by ultracentrifugation and size/number were determined by the Nano‐sight tracking system. Diabetic ssEVs significantly impaired tube formation and migration abilities of human MVECs. Furthermore, local transplantation of diabetic ssEVs strikingly reduced blood perfusion and capillary/arteriole density in ischemic hind limb of wildtype C57BL/6J mice. Diabetic ssEVs decreased secretion/expression of several pro‐angiogenic factors in human MVECs. Mechanistically, expression of enhancer of zest homolog 2 (EZH2), the major methyltransferase responsible for catalyzing H3K27me3 (a transcription repressive maker), and H3K27me3 was increased in MVECs from db/db mice. Diabetic ssEVs increased EZH2 and H3K27me3 expression/activity in human MVECs. Expression of EZH2 mRNA was increased in diabetic ssEVs. EZH2‐specific inhibitor significantly reversed diabetic ssEVs‐enhanced expression of EZH2 and H3K27me3, impaired expression of angiogenic factors, and improved blood perfusion and vessel density in ischemic hind limb of C57BL/6J mice. Finally, EZH2 inactivation repressed diabetic ssEVs‐induced H3K27me3 expression at promoter of pro‐angiogenic genes. Conclusions Diabetic ssEVs impair the angiogenic property of MVECs via, at least partially, transferring EZH2 mRNA to MVECs, thus inducing the epigenetic mechanism involving EZH2‐enhanced expression of H3K27me3 and consequent silencing of pro‐angiogenic genes. Our findings unravel the cellular mechanism and expand the scope of bloodborne substances that impair MVEC function in diabetes mellitus.

scholarly journals The Role of Mesenchymal Stromal Cells-Derived Small Extracellular Vesicles in Diabetes and Its Chronic Complications

2021 ◽  
Vol 12 ◽  
Author(s):  
Fu-Xing-Zi Li ◽  
Xiao Lin ◽  
Feng Xu ◽  
Su-Kang Shan ◽  
Bei Guo ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Extracellular Vesicles ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Molecular Mechanisms ◽  
Membrane Vesicles ◽  
Non Coding Rna ◽  
Multiple Differentiation ◽  
Treatment Of Diabetes

Mesenchymal stromal cells (MSCs) are applied in regenerative medicine of several tissues and organs nowadays by virtue of their self-renewal capabilities, multiple differentiation capacity, potent immunomodulatory properties, and their ability to be favourably cultured and manipulated. With the continuous development of “cell-free therapy” research, MSC-derived small extracellular vesicles (MSC-sEVs) have increasingly become a research hotspot in the treatment of various diseases. Small extracellular vesicles (SEVs) are membrane vesicles with diameters of 30 to 150 nm that mediate signal transduction between adjacent or distal cells or organs by delivering non-coding RNA, protein, and DNA. The contents and effects of sEVs vary depending on the properties of the originating cell. In recent years, MSC-sEVs have been found to play an important role in the occurrence and development of diabetes mellitus as a new way of communication between cells. Diabetes mellitus is a common metabolic disease in clinic. Its complications of the heart, brain, kidney, eyes, and peripheral nerves are a serious threat to human health and has been a hot issue for clinicians. MSC-sEVs could be applied to repair or prevent damage from the complications of diabetes mellitus through anti-inflammatory effects, reduction of endoplasmic reticulum-related protein stress, polarization of M2 macrophages, and increasing autophagy. Therefore, we highly recommend that MSC-sEVs-based therapies to treat diabetes mellitus and its chronic complication be further explored. The analysis of the role and molecular mechanisms of MSC-sEVs in diabetes and its related complications will provide new idea and insights for the prevention and treatment of diabetes.

Role Of Ultrasonography and Renal Doppler for Renal Changes in Diabetes Mellitus

2012 ◽  
Vol 3 (1) ◽  
pp. 315-316
Author(s):  
Dr. Sanay Prajapati ◽  
◽  
Dr. Divyesh Patel ◽  
Dr. Jay Panchal ◽  
Dr. Viplav Gndhi ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Renal Changes ◽  
Renal Doppler

Ghrelin and Obesity-An Update

2017 ◽  
Vol 9 (1) ◽  
Author(s):  
Gandhi M. ◽  
Swaminathan S.
Keyword(s):  
Diabetes Mellitus ◽  
Cardiac Output ◽  
Energy Balance ◽  
Vascular Resistance ◽  
The Body ◽  
Ghrelin Receptor ◽  
Type2 Diabetes ◽  
Type2 Diabetes Mellitus ◽  
Natural Hormones

Ghrelin as human natural hormones is involved in fundamental regulatory process of eating and energy balance. It is a stomach derived hormone that acts as at the ghrelin receptor in multiple tissues throughout to the body. Its properties includes increasing appetite, decreasing systemic inflammation, decreasing vascular resistance ,increasing cardiac output, increasing glucose and IGF-1 levels, Hence it may play a significant role in Diabetes mellitus. Many studies have linked ghrelin to obesity and this paper is an attempt to bring out recent findings on the role of ghrelin in Diabetes Mellitus, particularly type2 Diabetes mellitus.

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