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...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-11-01
|
| Series: | Biomedicines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2227-9059/10/11/2782 |
| _version_ | 1827647186388647936 |
|---|---|
| author | Ana Filipa Martins Ana Catarina Neto Adriana Raquel Rodrigues Sandra Marisa Oliveira Cláudia Sousa-Mendes Adelino Leite-Moreira Alexandra Maria Gouveia Henrique Almeida Delminda Neves |
| author_facet | Ana Filipa Martins Ana Catarina Neto Adriana Raquel Rodrigues Sandra Marisa Oliveira Cláudia Sousa-Mendes Adelino Leite-Moreira Alexandra Maria Gouveia Henrique Almeida Delminda Neves |
| author_sort | Ana Filipa Martins |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-09T19:15:40Z |
| format | Article |
| id | doaj.art-e4ec2b7bf18b4def9ac2b00b682e253c |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-09T19:15:40Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-e4ec2b7bf18b4def9ac2b00b682e253c2023-11-24T03:50:37ZengMDPI AGBiomedicines2227-90592022-11-011011278210.3390/biomedicines10112782Metformin Prevents Endothelial Dysfunction in Endometriosis through Downregulation of ET-1 and Upregulation of eNOSAna Filipa Martins0Ana Catarina Neto1Adriana Raquel Rodrigues2Sandra Marisa Oliveira3Cláudia Sousa-Mendes4Adelino Leite-Moreira5Alexandra Maria Gouveia6Henrique Almeida7Delminda Neves8Department of Biomedicine-Experimental Biology Unit, Faculty of Medicine of the University of Porto, 4200-319 Porto, PortugalDepartment of Biomedicine-Experimental Biology Unit, Faculty of Medicine of the University of Porto, 4200-319 Porto, PortugalDepartment of Biomedicine-Experimental Biology Unit, Faculty of Medicine of the University of Porto, 4200-319 Porto, PortugalCardiovascular R&D Centre-UnIC@RISE, Department of Surgery and Physiology, Faculty of Medicine of the University of Porto, 4200-319 Porto, PortugalCardiovascular R&D Centre-UnIC@RISE, Department of Surgery and Physiology, Faculty of Medicine of the University of Porto, 4200-319 Porto, PortugalCardiovascular R&D Centre-UnIC@RISE, Department of Surgery and Physiology, Faculty of Medicine of the University of Porto, 4200-319 Porto, PortugalDepartment of Biomedicine-Experimental Biology Unit, Faculty of Medicine of the University of Porto, 4200-319 Porto, PortugalDepartment of Biomedicine-Experimental Biology Unit, Faculty of Medicine of the University of Porto, 4200-319 Porto, PortugalDepartment of Biomedicine-Experimental Biology Unit, Faculty of Medicine of the University of Porto, 4200-319 Porto, PortugalThis 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.https://www.mdpi.com/2227-9059/10/11/2782cardiac fibrosisendometriosisendothelial dysfunctioninflammationmetformin |
| spellingShingle | Ana Filipa Martins Ana Catarina Neto Adriana Raquel Rodrigues Sandra Marisa Oliveira Cláudia Sousa-Mendes Adelino Leite-Moreira Alexandra Maria Gouveia Henrique Almeida Delminda Neves Metformin Prevents Endothelial Dysfunction in Endometriosis through Downregulation of ET-1 and Upregulation of eNOS Biomedicines cardiac fibrosis endometriosis endothelial dysfunction inflammation metformin |
| 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 | cardiac fibrosis endometriosis endothelial dysfunction inflammation metformin |
| url | https://www.mdpi.com/2227-9059/10/11/2782 |
| work_keys_str_mv | AT anafilipamartins metforminpreventsendothelialdysfunctioninendometriosisthroughdownregulationofet1andupregulationofenos AT anacatarinaneto metforminpreventsendothelialdysfunctioninendometriosisthroughdownregulationofet1andupregulationofenos AT adrianaraquelrodrigues metforminpreventsendothelialdysfunctioninendometriosisthroughdownregulationofet1andupregulationofenos AT sandramarisaoliveira metforminpreventsendothelialdysfunctioninendometriosisthroughdownregulationofet1andupregulationofenos AT claudiasousamendes metforminpreventsendothelialdysfunctioninendometriosisthroughdownregulationofet1andupregulationofenos AT adelinoleitemoreira metforminpreventsendothelialdysfunctioninendometriosisthroughdownregulationofet1andupregulationofenos AT alexandramariagouveia metforminpreventsendothelialdysfunctioninendometriosisthroughdownregulationofet1andupregulationofenos AT henriquealmeida metforminpreventsendothelialdysfunctioninendometriosisthroughdownregulationofet1andupregulationofenos AT delmindaneves metforminpreventsendothelialdysfunctioninendometriosisthroughdownregulationofet1andupregulationofenos |