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Mesenchymal stem cells promote type 2 macrophage polarization to ameliorate the myocardial injury caused by diabetic cardiomyopathy
BACKGROUND: Diabetic cardiomyopathy (DCM) is a common complication of diabetes and is characterized by chronic myocardial inflammation. Mesenchymal stem cell (MSC) infusions have recently been suggested to alleviate myocardial injury and ameliorate cardiac function. However, few studies have focused...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6683374/ https://www.ncbi.nlm.nih.gov/pubmed/31382970 http://dx.doi.org/10.1186/s12967-019-1999-8 |
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author | Jin, Liyuan Deng, Zihui Zhang, Jinying Yang, Chen Liu, Jiejie Han, Weidong Ye, Ping Si, Yiling Chen, Guanghui |
author_facet | Jin, Liyuan Deng, Zihui Zhang, Jinying Yang, Chen Liu, Jiejie Han, Weidong Ye, Ping Si, Yiling Chen, Guanghui |
author_sort | Jin, Liyuan |
collection | PubMed |
description | BACKGROUND: Diabetic cardiomyopathy (DCM) is a common complication of diabetes and is characterized by chronic myocardial inflammation. Mesenchymal stem cell (MSC) infusions have recently been suggested to alleviate myocardial injury and ameliorate cardiac function. However, few studies have focused on the effects of MSCs in DCM. Therefore, we explored the effects of MSC-regulated macrophage polarization on myocardial repair in DCM. METHODS: A DCM rat model was induced by a high-fat diet and streptozotocin (STZ) administration and infused 4 times with MSCs. Rat blood and heart tissue were analyzed for blood glucose levels, lipid levels, echocardiography, histopathology, macrophage phenotype ratios and inflammatory cytokines, respectively. We mimicked chronic inflammation in vitro by inducing peritoneal macrophages with high glucose and LPS, then cocultured these macrophages with MSCs to explore the specific mechanism of MSCs on macrophage polarization. RESULTS: DCM rats exhibited abnormal blood glucose levels and lipid metabolism, cardiac inflammation and dysfunction. MSC infusion ameliorated metabolic abnormalities and preserved cardiac structure and function in DCM rats. Moreover, MSC infusion significantly increased the M2 phenotype macrophages and alleviated cardiac inflammation. Interestingly, this in vitro study revealed that the MSCs pretreated with a COX-2 inhibitor had little effect on M2 macrophage polarization, but this phenomenon could be reversed by adding prostaglandin E2 (PGE2). CONCLUSIONS: Our results suggested that MSC infusions can protect against cardiac injury in DCM rats. The underlying mechanisms may include MSC-enhanced M2 macrophage polarization via the COX-2-PGE2 pathway. |
format | Online Article Text |
id | pubmed-6683374 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-66833742019-08-09 Mesenchymal stem cells promote type 2 macrophage polarization to ameliorate the myocardial injury caused by diabetic cardiomyopathy Jin, Liyuan Deng, Zihui Zhang, Jinying Yang, Chen Liu, Jiejie Han, Weidong Ye, Ping Si, Yiling Chen, Guanghui J Transl Med Research BACKGROUND: Diabetic cardiomyopathy (DCM) is a common complication of diabetes and is characterized by chronic myocardial inflammation. Mesenchymal stem cell (MSC) infusions have recently been suggested to alleviate myocardial injury and ameliorate cardiac function. However, few studies have focused on the effects of MSCs in DCM. Therefore, we explored the effects of MSC-regulated macrophage polarization on myocardial repair in DCM. METHODS: A DCM rat model was induced by a high-fat diet and streptozotocin (STZ) administration and infused 4 times with MSCs. Rat blood and heart tissue were analyzed for blood glucose levels, lipid levels, echocardiography, histopathology, macrophage phenotype ratios and inflammatory cytokines, respectively. We mimicked chronic inflammation in vitro by inducing peritoneal macrophages with high glucose and LPS, then cocultured these macrophages with MSCs to explore the specific mechanism of MSCs on macrophage polarization. RESULTS: DCM rats exhibited abnormal blood glucose levels and lipid metabolism, cardiac inflammation and dysfunction. MSC infusion ameliorated metabolic abnormalities and preserved cardiac structure and function in DCM rats. Moreover, MSC infusion significantly increased the M2 phenotype macrophages and alleviated cardiac inflammation. Interestingly, this in vitro study revealed that the MSCs pretreated with a COX-2 inhibitor had little effect on M2 macrophage polarization, but this phenomenon could be reversed by adding prostaglandin E2 (PGE2). CONCLUSIONS: Our results suggested that MSC infusions can protect against cardiac injury in DCM rats. The underlying mechanisms may include MSC-enhanced M2 macrophage polarization via the COX-2-PGE2 pathway. BioMed Central 2019-08-05 /pmc/articles/PMC6683374/ /pubmed/31382970 http://dx.doi.org/10.1186/s12967-019-1999-8 Text en © The Author(s) 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Jin, Liyuan Deng, Zihui Zhang, Jinying Yang, Chen Liu, Jiejie Han, Weidong Ye, Ping Si, Yiling Chen, Guanghui Mesenchymal stem cells promote type 2 macrophage polarization to ameliorate the myocardial injury caused by diabetic cardiomyopathy |
title | Mesenchymal stem cells promote type 2 macrophage polarization to ameliorate the myocardial injury caused by diabetic cardiomyopathy |
title_full | Mesenchymal stem cells promote type 2 macrophage polarization to ameliorate the myocardial injury caused by diabetic cardiomyopathy |
title_fullStr | Mesenchymal stem cells promote type 2 macrophage polarization to ameliorate the myocardial injury caused by diabetic cardiomyopathy |
title_full_unstemmed | Mesenchymal stem cells promote type 2 macrophage polarization to ameliorate the myocardial injury caused by diabetic cardiomyopathy |
title_short | Mesenchymal stem cells promote type 2 macrophage polarization to ameliorate the myocardial injury caused by diabetic cardiomyopathy |
title_sort | mesenchymal stem cells promote type 2 macrophage polarization to ameliorate the myocardial injury caused by diabetic cardiomyopathy |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6683374/ https://www.ncbi.nlm.nih.gov/pubmed/31382970 http://dx.doi.org/10.1186/s12967-019-1999-8 |
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