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Sirt6 mRNA-incorporated endothelial microparticles (EMPs) attenuates DM patient-derived EMP-induced endothelial dysfunction

BACKGROUND: Endothelial microparticles (EMPs) are small vesicles released by endothelial cells (ECs); they are considered biomarkers for endothelial dysfunction and therapeutic targets in diabetes-related vascular disease. Sirtuins have also been shown to play important roles in diabetes by regulati...

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Autores principales: Jing, Tong, Ya-Shu, Kuang, Xue-Jun, Wang, Han-Jing, Hou, Yan, Lai, Yi-An, Yao, Fei, Chen, Xue-Bo, Liu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5768405/
https://www.ncbi.nlm.nih.gov/pubmed/29371988
http://dx.doi.org/10.18632/oncotarget.23259
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author Jing, Tong
Ya-Shu, Kuang
Xue-Jun, Wang
Han-Jing, Hou
Yan, Lai
Yi-An, Yao
Fei, Chen
Xue-Bo, Liu
author_facet Jing, Tong
Ya-Shu, Kuang
Xue-Jun, Wang
Han-Jing, Hou
Yan, Lai
Yi-An, Yao
Fei, Chen
Xue-Bo, Liu
author_sort Jing, Tong
collection PubMed
description BACKGROUND: Endothelial microparticles (EMPs) are small vesicles released by endothelial cells (ECs); they are considered biomarkers for endothelial dysfunction and therapeutic targets in diabetes-related vascular disease. Sirtuins have also been shown to play important roles in diabetes by regulating endothelial dysfunction. However, the effect of sirtuin-incorporated EMPs on their parental ECs remains unknown. AIM: The present study aims to investigate the diagnostic value of EMPs in diabetes and detect the protective effects of sirtuin 6 (Sirt6) mRNA -incorporated EMPs on endothelial dysfunction. METHODS: EMPs were prepared from cultured HUVECs and venous blood from patients with diabetes (n=10) and from healthy volunteers (n=6) after sequential centrifugation. Adv-Sirt6 or Sirt6 siRNA was used to alter Sirt6 expression. EC angiogenesis, inflammatory phenotypes, nitric oxide (NO) formation and eNOS phosphorylation were used to evaluate endothelial dysfunction. RESULTS: The levels of EMPs in diabetic patients and high glucose-cultured HUVECs are high, whereas Sirt6 expression in plasma and EMPs is low. EMPs generated from diabetic patients or high glucose-cultured HUVECs increase inflammatory chemokine release and blunt EC angiogenesis. Furthermore, EMPs enriched with Sirt6 mRNA induces EC angiogenesis, increases eNOS phosphorylation and impedes inflammatory chemokine release. Inhibition of Sirt6 mRNA expression in EMPs by siRNA hinders angiogenesis and eNOS phosphorylation but increases cellular inflammation. CONCLUSION: The Sirt6 mRNA-carrying EMPs may ameliorate endothelial dysfunction in diabetic patients.
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spelling pubmed-57684052018-01-25 Sirt6 mRNA-incorporated endothelial microparticles (EMPs) attenuates DM patient-derived EMP-induced endothelial dysfunction Jing, Tong Ya-Shu, Kuang Xue-Jun, Wang Han-Jing, Hou Yan, Lai Yi-An, Yao Fei, Chen Xue-Bo, Liu Oncotarget Research Paper BACKGROUND: Endothelial microparticles (EMPs) are small vesicles released by endothelial cells (ECs); they are considered biomarkers for endothelial dysfunction and therapeutic targets in diabetes-related vascular disease. Sirtuins have also been shown to play important roles in diabetes by regulating endothelial dysfunction. However, the effect of sirtuin-incorporated EMPs on their parental ECs remains unknown. AIM: The present study aims to investigate the diagnostic value of EMPs in diabetes and detect the protective effects of sirtuin 6 (Sirt6) mRNA -incorporated EMPs on endothelial dysfunction. METHODS: EMPs were prepared from cultured HUVECs and venous blood from patients with diabetes (n=10) and from healthy volunteers (n=6) after sequential centrifugation. Adv-Sirt6 or Sirt6 siRNA was used to alter Sirt6 expression. EC angiogenesis, inflammatory phenotypes, nitric oxide (NO) formation and eNOS phosphorylation were used to evaluate endothelial dysfunction. RESULTS: The levels of EMPs in diabetic patients and high glucose-cultured HUVECs are high, whereas Sirt6 expression in plasma and EMPs is low. EMPs generated from diabetic patients or high glucose-cultured HUVECs increase inflammatory chemokine release and blunt EC angiogenesis. Furthermore, EMPs enriched with Sirt6 mRNA induces EC angiogenesis, increases eNOS phosphorylation and impedes inflammatory chemokine release. Inhibition of Sirt6 mRNA expression in EMPs by siRNA hinders angiogenesis and eNOS phosphorylation but increases cellular inflammation. CONCLUSION: The Sirt6 mRNA-carrying EMPs may ameliorate endothelial dysfunction in diabetic patients. Impact Journals LLC 2017-12-15 /pmc/articles/PMC5768405/ /pubmed/29371988 http://dx.doi.org/10.18632/oncotarget.23259 Text en Copyright: © 2017 Jing et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Jing, Tong
Ya-Shu, Kuang
Xue-Jun, Wang
Han-Jing, Hou
Yan, Lai
Yi-An, Yao
Fei, Chen
Xue-Bo, Liu
Sirt6 mRNA-incorporated endothelial microparticles (EMPs) attenuates DM patient-derived EMP-induced endothelial dysfunction
title Sirt6 mRNA-incorporated endothelial microparticles (EMPs) attenuates DM patient-derived EMP-induced endothelial dysfunction
title_full Sirt6 mRNA-incorporated endothelial microparticles (EMPs) attenuates DM patient-derived EMP-induced endothelial dysfunction
title_fullStr Sirt6 mRNA-incorporated endothelial microparticles (EMPs) attenuates DM patient-derived EMP-induced endothelial dysfunction
title_full_unstemmed Sirt6 mRNA-incorporated endothelial microparticles (EMPs) attenuates DM patient-derived EMP-induced endothelial dysfunction
title_short Sirt6 mRNA-incorporated endothelial microparticles (EMPs) attenuates DM patient-derived EMP-induced endothelial dysfunction
title_sort sirt6 mrna-incorporated endothelial microparticles (emps) attenuates dm patient-derived emp-induced endothelial dysfunction
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5768405/
https://www.ncbi.nlm.nih.gov/pubmed/29371988
http://dx.doi.org/10.18632/oncotarget.23259
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