Metformin Prevents Endothelial Dysfunction in Endometriosis through Downregulation of ET-1 and Upregulation of eNOS Article Swipe
Ana Filipa Martins
,
Ana Catarina Neto
,
Adriana R. Rodrigues
,
Sandra Marisa Oliveira
,
Cláudia Sousa-Mendes
,
Adelino Leite‐Moreira
,
Alexandra Gouveia
,
Henrique Almeida
,
Delminda Neves
·
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.3390/biomedicines10112782
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.3390/biomedicines10112782
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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Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.3390/biomedicines10112782
- https://www.mdpi.com/2227-9059/10/11/2782/pdf?version=1668155315
- OA Status
- gold
- Cited By
- 6
- References
- 60
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4308125628
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4308125628Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.3390/biomedicines10112782Digital Object Identifier
- Title
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Metformin Prevents Endothelial Dysfunction in Endometriosis through Downregulation of ET-1 and Upregulation of eNOSWork title
- Type
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articleOpenAlex work type
- Language
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enPrimary language
- Publication year
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2022Year of publication
- Publication date
-
2022-11-01Full publication date if available
- Authors
-
Ana Filipa Martins, Ana Catarina Neto, Adriana R. Rodrigues, Sandra Marisa Oliveira, Cláudia Sousa-Mendes, Adelino Leite‐Moreira, Alexandra Gouveia, Henrique Almeida, Delminda NevesList of authors in order
- Landing page
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https://doi.org/10.3390/biomedicines10112782Publisher landing page
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https://www.mdpi.com/2227-9059/10/11/2782/pdf?version=1668155315Direct link to full text PDF
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YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
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https://www.mdpi.com/2227-9059/10/11/2782/pdf?version=1668155315Direct OA link when available
- Concepts
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Metformin, Enos, Endometriosis, Fibrosis, Medicine, Sirius Red, Angiogenesis, Downregulation and upregulation, Internal medicine, Endothelial dysfunction, Endocrinology, Nitric oxide, Nitric oxide synthase, Chemistry, Diabetes mellitus, Gene, BiochemistryTop concepts (fields/topics) attached by OpenAlex
- Cited by
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6Total citation count in OpenAlex
- Citations by year (recent)
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2025: 2, 2024: 3, 2023: 1Per-year citation counts (last 5 years)
- References (count)
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60Number of works referenced by this work
- Related works (count)
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10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.B6CBA/F1 | 30 |
| abstract_inverted_index.Compared | 121 |
| abstract_inverted_index.However, | 160 |
| abstract_inverted_index.MIR16-1, | 93 |
| abstract_inverted_index.MIR199a, | 92, 174 |
| abstract_inverted_index.MIR200a, | 97 |
| abstract_inverted_index.assessed | 55, 115 |
| abstract_inverted_index.detected | 75 |
| abstract_inverted_index.evaluate | 4 |
| abstract_inverted_index.fibrosis | 60, 136, 208 |
| abstract_inverted_index.increase | 202 |
| abstract_inverted_index.mitigate | 164, 200 |
| abstract_inverted_index.pathways | 20 |
| abstract_inverted_index.reducing | 188 |
| abstract_inverted_index.staining | 58 |
| abstract_inverted_index.summary, | 191 |
| abstract_inverted_index.M-treated | 126 |
| abstract_inverted_index.Metformin | 42 |
| abstract_inverted_index.Real-Time | 105 |
| abstract_inverted_index.Treatment | 140 |
| abstract_inverted_index.blotting. | 91 |
| abstract_inverted_index.decreased | 178 |
| abstract_inverted_index.function, | 15 |
| abstract_inverted_index.increased | 137 |
| abstract_inverted_index.metformin | 9, 112, 144, 161, 192 |
| abstract_inverted_index.performed | 88 |
| abstract_inverted_index.presented | 128 |
| abstract_inverted_index.staining. | 63 |
| abstract_inverted_index.treatment | 7 |
| abstract_inverted_index.altogether | 187 |
| abstract_inverted_index.diminished | 193 |
| abstract_inverted_index.equivalent | 185 |
| abstract_inverted_index.expression | 154, 166, 172, 205 |
| abstract_inverted_index.quantified | 103 |
| abstract_inverted_index.structure, | 13 |
| abstract_inverted_index.surgically | 27 |
| abstract_inverted_index.dysfunction | 196 |
| abstract_inverted_index.endothelial | 14, 195 |
| abstract_inverted_index.incremented | 168 |
| abstract_inverted_index.interaction | 108 |
| abstract_inverted_index.morphologic | 12 |
| abstract_inverted_index.upregulates | 152 |
| abstract_inverted_index.inflammation | 17 |
| abstract_inverted_index.Endometriosis | 44 |
| abstract_inverted_index.angiogenesis, | 16 |
| abstract_inverted_index.comparatively | 155 |
| abstract_inverted_index.downregulates | 149 |
| abstract_inverted_index.endometriosis | 110, 142 |
| abstract_inverted_index.significantly | 167 |
| abstract_inverted_index.cardiomyocytes | 53 |
| abstract_inverted_index.endometriosis, | 180 |
| abstract_inverted_index.endometriosis. | 29, 139, 170, 212 |
| abstract_inverted_index.synthases-iNOS | 67 |
| abstract_inverted_index.Picrosirius-Red | 62 |
| abstract_inverted_index.cardiomyocytes. | 134 |
| abstract_inverted_index.cross-sectional | 50, 131 |
| abstract_inverted_index.cardioprotection. | 189 |
| abstract_inverted_index.Hematoxylin–Eosin | 57 |
| abstract_inverted_index.Semi-quantification | 78 |
| abstract_inverted_index.immunofluorescence. | 77 |
| abstract_inverted_index.oxidation-responsive | 19 |
| abstract_inverted_index.Metformin/Endometriosis | 47 |
| abstract_inverted_index.endometriosis-associated | 194 |
| cited_by_percentile_year.max | 97 |
| cited_by_percentile_year.min | 89 |
| corresponding_author_ids | https://openalex.org/A5055236064 |
| countries_distinct_count | 1 |
| institutions_distinct_count | 9 |
| corresponding_institution_ids | https://openalex.org/I182534213, https://openalex.org/I4210158732 |
| citation_normalized_percentile.value | 0.77479757 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | False |