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Liraglutide preserves CD34(+) stem cells from dysfunction Induced by high glucose exposure
BACKGROUND: Glucagon like peptide-1 receptor agonists (GLP-1RAs) have shown to reduce mortality and cardiovascular events in patients with type 2 diabetes mellitus (T2DM). Since the impairment in number and function of vasculotrophic circulating CD34(+) hematopoietic stem progenitor cells (HSPCs) in...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8994898/ https://www.ncbi.nlm.nih.gov/pubmed/35397526 http://dx.doi.org/10.1186/s12933-022-01486-9 |
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author | Sforza, Annalisa Vigorelli, Vera Rurali, Erica Perrucci, Gianluca Lorenzo Gambini, Elisa Arici, Martina Metallo, Alessia Rinaldi, Raffaella Fiorina, Paolo Barbuti, Andrea Raucci, Angela Sacco, Elena Rocchetti, Marcella Pompilio, Giulio Genovese, Stefano Vinci, Maria Cristina |
author_facet | Sforza, Annalisa Vigorelli, Vera Rurali, Erica Perrucci, Gianluca Lorenzo Gambini, Elisa Arici, Martina Metallo, Alessia Rinaldi, Raffaella Fiorina, Paolo Barbuti, Andrea Raucci, Angela Sacco, Elena Rocchetti, Marcella Pompilio, Giulio Genovese, Stefano Vinci, Maria Cristina |
author_sort | Sforza, Annalisa |
collection | PubMed |
description | BACKGROUND: Glucagon like peptide-1 receptor agonists (GLP-1RAs) have shown to reduce mortality and cardiovascular events in patients with type 2 diabetes mellitus (T2DM). Since the impairment in number and function of vasculotrophic circulating CD34(+) hematopoietic stem progenitor cells (HSPCs) in T2D has been reported to increase cardiovascular (CV) risk, we hypothesized that one of the mechanisms whereby GLP-1 RAs exert CV protective effects may be related to the ability to improve CD34(+) HSPC function. METHODS: In cord blood (CB)-derived CD34(+) HSPC, the expression of GLP-1 receptor (GLP-1R) mRNA, receptor protein and intracellular signaling was evaluated by RT-qPCR and Western Blot respectively. CD34(+) HSPCs were exposed to high glucose (HG) condition and GLP-1RA liraglutide (LIRA) was added before as well as after functional impairment. Proliferation, CXCR4/SDF-1α axis activity and intracellular ROS production of CD34(+) HSPC were evaluated. RESULTS: CD34(+) HSPCs express GLP-1R at transcriptional and protein level. LIRA treatment prevented and rescued HSPC proliferation, CXCR4/SDF-1α axis activity and metabolic imbalance from HG-induced impairment. LIRA stimulation promoted intracellular cAMP accumulation as well as ERK1/2 and AKT signaling activation. The selective GLP-1R antagonist exendin (9–39) abrogated LIRA-dependent ERK1/2 and AKT phosphorylation along with the related protective effects. CONCLUSION: We provided the first evidence that CD34(+) HSPC express GLP-1R and that LIRA can favorably impact on cell dysfunction due to HG exposure. These findings open new perspectives on the favorable CV effects of GLP-1 RAs in T2DM patients. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12933-022-01486-9. |
format | Online Article Text |
id | pubmed-8994898 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-89948982022-04-11 Liraglutide preserves CD34(+) stem cells from dysfunction Induced by high glucose exposure Sforza, Annalisa Vigorelli, Vera Rurali, Erica Perrucci, Gianluca Lorenzo Gambini, Elisa Arici, Martina Metallo, Alessia Rinaldi, Raffaella Fiorina, Paolo Barbuti, Andrea Raucci, Angela Sacco, Elena Rocchetti, Marcella Pompilio, Giulio Genovese, Stefano Vinci, Maria Cristina Cardiovasc Diabetol Original Investigation BACKGROUND: Glucagon like peptide-1 receptor agonists (GLP-1RAs) have shown to reduce mortality and cardiovascular events in patients with type 2 diabetes mellitus (T2DM). Since the impairment in number and function of vasculotrophic circulating CD34(+) hematopoietic stem progenitor cells (HSPCs) in T2D has been reported to increase cardiovascular (CV) risk, we hypothesized that one of the mechanisms whereby GLP-1 RAs exert CV protective effects may be related to the ability to improve CD34(+) HSPC function. METHODS: In cord blood (CB)-derived CD34(+) HSPC, the expression of GLP-1 receptor (GLP-1R) mRNA, receptor protein and intracellular signaling was evaluated by RT-qPCR and Western Blot respectively. CD34(+) HSPCs were exposed to high glucose (HG) condition and GLP-1RA liraglutide (LIRA) was added before as well as after functional impairment. Proliferation, CXCR4/SDF-1α axis activity and intracellular ROS production of CD34(+) HSPC were evaluated. RESULTS: CD34(+) HSPCs express GLP-1R at transcriptional and protein level. LIRA treatment prevented and rescued HSPC proliferation, CXCR4/SDF-1α axis activity and metabolic imbalance from HG-induced impairment. LIRA stimulation promoted intracellular cAMP accumulation as well as ERK1/2 and AKT signaling activation. The selective GLP-1R antagonist exendin (9–39) abrogated LIRA-dependent ERK1/2 and AKT phosphorylation along with the related protective effects. CONCLUSION: We provided the first evidence that CD34(+) HSPC express GLP-1R and that LIRA can favorably impact on cell dysfunction due to HG exposure. These findings open new perspectives on the favorable CV effects of GLP-1 RAs in T2DM patients. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12933-022-01486-9. BioMed Central 2022-04-09 /pmc/articles/PMC8994898/ /pubmed/35397526 http://dx.doi.org/10.1186/s12933-022-01486-9 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Original Investigation Sforza, Annalisa Vigorelli, Vera Rurali, Erica Perrucci, Gianluca Lorenzo Gambini, Elisa Arici, Martina Metallo, Alessia Rinaldi, Raffaella Fiorina, Paolo Barbuti, Andrea Raucci, Angela Sacco, Elena Rocchetti, Marcella Pompilio, Giulio Genovese, Stefano Vinci, Maria Cristina Liraglutide preserves CD34(+) stem cells from dysfunction Induced by high glucose exposure |
title | Liraglutide preserves CD34(+) stem cells from dysfunction Induced by high glucose exposure |
title_full | Liraglutide preserves CD34(+) stem cells from dysfunction Induced by high glucose exposure |
title_fullStr | Liraglutide preserves CD34(+) stem cells from dysfunction Induced by high glucose exposure |
title_full_unstemmed | Liraglutide preserves CD34(+) stem cells from dysfunction Induced by high glucose exposure |
title_short | Liraglutide preserves CD34(+) stem cells from dysfunction Induced by high glucose exposure |
title_sort | liraglutide preserves cd34(+) stem cells from dysfunction induced by high glucose exposure |
topic | Original Investigation |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8994898/ https://www.ncbi.nlm.nih.gov/pubmed/35397526 http://dx.doi.org/10.1186/s12933-022-01486-9 |
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