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Sitagliptin Stimulates Endothelial Progenitor Cells to Induce Endothelialization in Aneurysm Necks Through the SDF-1/CXCR4/NRF2 Signaling Pathway

Aneurysm (AN) embolization is an important treatment for cerebral aneurysms. The endothelialization of the aneurysm neck is crucial for preventing aneurysm recurrence. Sitagliptin is a therapeutic drug for diabetes that has been reported to have cardiovascular-protective effects. This study investig...

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Autores principales: Yu, Guo, Liu, Peixi, Shi, Yuan, Li, Sichen, Liu, Yingjun, Zhu, Wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6988800/
https://www.ncbi.nlm.nih.gov/pubmed/32038475
http://dx.doi.org/10.3389/fendo.2019.00823
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author Yu, Guo
Liu, Peixi
Shi, Yuan
Li, Sichen
Liu, Yingjun
Zhu, Wei
author_facet Yu, Guo
Liu, Peixi
Shi, Yuan
Li, Sichen
Liu, Yingjun
Zhu, Wei
author_sort Yu, Guo
collection PubMed
description Aneurysm (AN) embolization is an important treatment for cerebral aneurysms. The endothelialization of the aneurysm neck is crucial for preventing aneurysm recurrence. Sitagliptin is a therapeutic drug for diabetes that has been reported to have cardiovascular-protective effects. This study investigated the effect of sitagliptin on endothelial progenitor cell (EPC) function and endothelialization of aneurysm necks after embolization. The effect of sitagliptin on aneurysm neck endothelialization was examined using a rat aneurysm embolization model. We isolated EPCs and used CCK-8 (Cell Counting Kit-8) and annexin V/PI to analyze the effect of sitagliptin on the proliferation and apoptosis of EPCs. The effects of sitagliptin on the migration and invasion of EPCs were examined using scratch and Transwell assays. The effect of sitagliptin on the angiogenic ability of EPCs was examined using a sprouting assay. Western blot analysis and ELISA were used to analyze the effect of sitagliptin on the expression of proangiogenic factors in EPCs. The in vivo results indicated that sitagliptin promoted endothelialization of the aneurysm neck and increased circulating EPCs and expression levels of SDF-1 and VEGF in peripheral blood. Sitagliptin promoted the proliferation, migration, invasion, and angiogenic abilities of EPCs. Western blot analysis and ELISA showed that sitagliptin promoted the expression of SDF-1 and VEGF in progenitor endothelial cells. Western blot assays showed that sitagliptin activated the expression of NRF2, which is dependent on the function of CXCR4. Furthermore, sitagliptin promoted progenitor endothelial cell migration, invasion and angiogenesis through the SDF-1/CXCR4/NRF2 signaling pathway. Additionally, progenitor endothelial cells expressed SDF-1 and VEGF. The promotion of endothelialization by sitagliptin provides an additional therapeutic option for preventing the recurrence of AN.
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spelling pubmed-69888002020-02-07 Sitagliptin Stimulates Endothelial Progenitor Cells to Induce Endothelialization in Aneurysm Necks Through the SDF-1/CXCR4/NRF2 Signaling Pathway Yu, Guo Liu, Peixi Shi, Yuan Li, Sichen Liu, Yingjun Zhu, Wei Front Endocrinol (Lausanne) Endocrinology Aneurysm (AN) embolization is an important treatment for cerebral aneurysms. The endothelialization of the aneurysm neck is crucial for preventing aneurysm recurrence. Sitagliptin is a therapeutic drug for diabetes that has been reported to have cardiovascular-protective effects. This study investigated the effect of sitagliptin on endothelial progenitor cell (EPC) function and endothelialization of aneurysm necks after embolization. The effect of sitagliptin on aneurysm neck endothelialization was examined using a rat aneurysm embolization model. We isolated EPCs and used CCK-8 (Cell Counting Kit-8) and annexin V/PI to analyze the effect of sitagliptin on the proliferation and apoptosis of EPCs. The effects of sitagliptin on the migration and invasion of EPCs were examined using scratch and Transwell assays. The effect of sitagliptin on the angiogenic ability of EPCs was examined using a sprouting assay. Western blot analysis and ELISA were used to analyze the effect of sitagliptin on the expression of proangiogenic factors in EPCs. The in vivo results indicated that sitagliptin promoted endothelialization of the aneurysm neck and increased circulating EPCs and expression levels of SDF-1 and VEGF in peripheral blood. Sitagliptin promoted the proliferation, migration, invasion, and angiogenic abilities of EPCs. Western blot analysis and ELISA showed that sitagliptin promoted the expression of SDF-1 and VEGF in progenitor endothelial cells. Western blot assays showed that sitagliptin activated the expression of NRF2, which is dependent on the function of CXCR4. Furthermore, sitagliptin promoted progenitor endothelial cell migration, invasion and angiogenesis through the SDF-1/CXCR4/NRF2 signaling pathway. Additionally, progenitor endothelial cells expressed SDF-1 and VEGF. The promotion of endothelialization by sitagliptin provides an additional therapeutic option for preventing the recurrence of AN. Frontiers Media S.A. 2019-11-26 /pmc/articles/PMC6988800/ /pubmed/32038475 http://dx.doi.org/10.3389/fendo.2019.00823 Text en Copyright © 2019 Yu, Liu, Shi, Li, Liu and Zhu. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Endocrinology
Yu, Guo
Liu, Peixi
Shi, Yuan
Li, Sichen
Liu, Yingjun
Zhu, Wei
Sitagliptin Stimulates Endothelial Progenitor Cells to Induce Endothelialization in Aneurysm Necks Through the SDF-1/CXCR4/NRF2 Signaling Pathway
title Sitagliptin Stimulates Endothelial Progenitor Cells to Induce Endothelialization in Aneurysm Necks Through the SDF-1/CXCR4/NRF2 Signaling Pathway
title_full Sitagliptin Stimulates Endothelial Progenitor Cells to Induce Endothelialization in Aneurysm Necks Through the SDF-1/CXCR4/NRF2 Signaling Pathway
title_fullStr Sitagliptin Stimulates Endothelial Progenitor Cells to Induce Endothelialization in Aneurysm Necks Through the SDF-1/CXCR4/NRF2 Signaling Pathway
title_full_unstemmed Sitagliptin Stimulates Endothelial Progenitor Cells to Induce Endothelialization in Aneurysm Necks Through the SDF-1/CXCR4/NRF2 Signaling Pathway
title_short Sitagliptin Stimulates Endothelial Progenitor Cells to Induce Endothelialization in Aneurysm Necks Through the SDF-1/CXCR4/NRF2 Signaling Pathway
title_sort sitagliptin stimulates endothelial progenitor cells to induce endothelialization in aneurysm necks through the sdf-1/cxcr4/nrf2 signaling pathway
topic Endocrinology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6988800/
https://www.ncbi.nlm.nih.gov/pubmed/32038475
http://dx.doi.org/10.3389/fendo.2019.00823
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