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Metformin Prevents Endothelial Dysfunction in Endometriosis through Downregulation of ET-1 and Upregulation of eNOS

This study aimed to evaluate if the treatment with metformin affects the morphologic structure, endothelial function, angiogenesis, inflammation and oxidation-responsive pathways in the heart of mice with surgically induced endometriosis. B6CBA/F1 mice (n = 37) were divided into four groups; Sham (S...

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Autores principales: Martins, Ana Filipa, Neto, Ana Catarina, Rodrigues, Adriana Raquel, Oliveira, Sandra Marisa, Sousa-Mendes, Cláudia, Leite-Moreira, Adelino, Gouveia, Alexandra Maria, Almeida, Henrique, Neves, Delminda
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9687337/
https://www.ncbi.nlm.nih.gov/pubmed/36359302
http://dx.doi.org/10.3390/biomedicines10112782
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author Martins, Ana Filipa
Neto, Ana Catarina
Rodrigues, Adriana Raquel
Oliveira, Sandra Marisa
Sousa-Mendes, Cláudia
Leite-Moreira, Adelino
Gouveia, Alexandra Maria
Almeida, Henrique
Neves, Delminda
author_facet Martins, Ana Filipa
Neto, Ana Catarina
Rodrigues, Adriana Raquel
Oliveira, Sandra Marisa
Sousa-Mendes, Cláudia
Leite-Moreira, Adelino
Gouveia, Alexandra Maria
Almeida, Henrique
Neves, Delminda
author_sort Martins, Ana Filipa
collection PubMed
description This study aimed to evaluate if the treatment with metformin affects the morphologic structure, endothelial function, angiogenesis, inflammation and oxidation-responsive pathways in the heart of mice with surgically induced endometriosis. B6CBA/F1 mice (n = 37) were divided into four groups; Sham (S), Metformin (M), Endometriosis (E) and Metformin/Endometriosis (ME). The cross-sectional area of cardiomyocytes was assessed after Hematoxylin–Eosin staining and fibrosis after Picrosirius-Red staining. ET-1, nitric oxide synthases-iNOS and eNOS, and VEGF and VEGFR-2 were detected by immunofluorescence. Semi-quantification of ET-1, eNOS, VEGF, NF-kB, Ikβα and KEAP-1 was performed by Western blotting. MIR199a, MIR16-1, MIR18a, MIR20a, MIR155, MIR200a, MIR342, MIR24-1 and MIR320a were quantified by Real-Time qPCR. The interaction of endometriosis and metformin effects was assessed by a two-way ANOVA test. Compared with the other groups, M-treated mice presented a higher cross-sectional area of cardiomyocytes. Heart fibrosis increased with endometriosis. Treatment of endometriosis with metformin in the ME group downregulates ET-1 and upregulates eNOS expression comparatively with the E group. However, metformin failed to mitigate NF-kB expression significantly incremented by endometriosis. The expression of MIR199a, MIR16-1 and MIR18a decreased with endometriosis, whereas MIR20a showed an equivalent trend, altogether reducing cardioprotection. In summary, metformin diminished endometriosis-associated endothelial dysfunction but did not mitigate the increase in NF-kB expression and cardiac fibrosis in mice with endometriosis.
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spelling pubmed-96873372022-11-25 Metformin Prevents Endothelial Dysfunction in Endometriosis through Downregulation of ET-1 and Upregulation of eNOS Martins, Ana Filipa Neto, Ana Catarina Rodrigues, Adriana Raquel Oliveira, Sandra Marisa Sousa-Mendes, Cláudia Leite-Moreira, Adelino Gouveia, Alexandra Maria Almeida, Henrique Neves, Delminda Biomedicines Article This study aimed to evaluate if the treatment with metformin affects the morphologic structure, endothelial function, angiogenesis, inflammation and oxidation-responsive pathways in the heart of mice with surgically induced endometriosis. B6CBA/F1 mice (n = 37) were divided into four groups; Sham (S), Metformin (M), Endometriosis (E) and Metformin/Endometriosis (ME). The cross-sectional area of cardiomyocytes was assessed after Hematoxylin–Eosin staining and fibrosis after Picrosirius-Red staining. ET-1, nitric oxide synthases-iNOS and eNOS, and VEGF and VEGFR-2 were detected by immunofluorescence. Semi-quantification of ET-1, eNOS, VEGF, NF-kB, Ikβα and KEAP-1 was performed by Western blotting. MIR199a, MIR16-1, MIR18a, MIR20a, MIR155, MIR200a, MIR342, MIR24-1 and MIR320a were quantified by Real-Time qPCR. The interaction of endometriosis and metformin effects was assessed by a two-way ANOVA test. Compared with the other groups, M-treated mice presented a higher cross-sectional area of cardiomyocytes. Heart fibrosis increased with endometriosis. Treatment of endometriosis with metformin in the ME group downregulates ET-1 and upregulates eNOS expression comparatively with the E group. However, metformin failed to mitigate NF-kB expression significantly incremented by endometriosis. The expression of MIR199a, MIR16-1 and MIR18a decreased with endometriosis, whereas MIR20a showed an equivalent trend, altogether reducing cardioprotection. In summary, metformin diminished endometriosis-associated endothelial dysfunction but did not mitigate the increase in NF-kB expression and cardiac fibrosis in mice with endometriosis. MDPI 2022-11-01 /pmc/articles/PMC9687337/ /pubmed/36359302 http://dx.doi.org/10.3390/biomedicines10112782 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Martins, Ana Filipa
Neto, Ana Catarina
Rodrigues, Adriana Raquel
Oliveira, Sandra Marisa
Sousa-Mendes, Cláudia
Leite-Moreira, Adelino
Gouveia, Alexandra Maria
Almeida, Henrique
Neves, Delminda
Metformin Prevents Endothelial Dysfunction in Endometriosis through Downregulation of ET-1 and Upregulation of eNOS
title Metformin Prevents Endothelial Dysfunction in Endometriosis through Downregulation of ET-1 and Upregulation of eNOS
title_full Metformin Prevents Endothelial Dysfunction in Endometriosis through Downregulation of ET-1 and Upregulation of eNOS
title_fullStr Metformin Prevents Endothelial Dysfunction in Endometriosis through Downregulation of ET-1 and Upregulation of eNOS
title_full_unstemmed Metformin Prevents Endothelial Dysfunction in Endometriosis through Downregulation of ET-1 and Upregulation of eNOS
title_short Metformin Prevents Endothelial Dysfunction in Endometriosis through Downregulation of ET-1 and Upregulation of eNOS
title_sort metformin prevents endothelial dysfunction in endometriosis through downregulation of et-1 and upregulation of enos
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9687337/
https://www.ncbi.nlm.nih.gov/pubmed/36359302
http://dx.doi.org/10.3390/biomedicines10112782
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