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Influence of diabetes mellitus on the pathological profile of aortic stenosis: a sex-based approach
BACKGROUND: Diabetes mellitus (DM) accelerates the progression of aortic stenosis (AS), but how their underlying molecular mechanisms interact is not clear. Moreover, whether DM contributes to clinically relevant sex-differences in AS is unknown. In this work we aim to characterize the sex-specific...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10583330/ https://www.ncbi.nlm.nih.gov/pubmed/37848892 http://dx.doi.org/10.1186/s12933-023-02009-w |
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author | Martín-Núñez, Ernesto Goñi-Olóriz, Miriam Matilla, Lara Garaikoetxea, Mattie Mourino-Alvarez, Laura Navarro, Adela Fernández-Celis, Amaya Tamayo, Ibai Gainza, Alicia Álvarez, Virginia Sádaba, Rafael Barderas, María G. Jover, Eva López-Andrés, Natalia |
author_facet | Martín-Núñez, Ernesto Goñi-Olóriz, Miriam Matilla, Lara Garaikoetxea, Mattie Mourino-Alvarez, Laura Navarro, Adela Fernández-Celis, Amaya Tamayo, Ibai Gainza, Alicia Álvarez, Virginia Sádaba, Rafael Barderas, María G. Jover, Eva López-Andrés, Natalia |
author_sort | Martín-Núñez, Ernesto |
collection | PubMed |
description | BACKGROUND: Diabetes mellitus (DM) accelerates the progression of aortic stenosis (AS), but how their underlying molecular mechanisms interact is not clear. Moreover, whether DM contributes to clinically relevant sex-differences in AS is unknown. In this work we aim to characterize the sex-specific profile of major pathological mechanisms fundamental to aortic valve (AV) degeneration in AS patients with or without concomitant DM. METHODS: 283 patients with severe AS undergoing surgical valve replacement (27.6% DM, 59.4% men) were recruited. Expression of pathological markers related to AS were thoroughly assessed in AVs and valve interstitial cells (VICs) according to sex and presence of DM. Complementary in vitro experiments in VICs in the presence of high-glucose levels (25 mM) for 24, 48 and 72 h were performed. RESULTS: Oxidative stress and metabolic dysfunction markers were increased in AVs from diabetic AS patients compared to non-diabetic patients in both sexes. However, disbalanced oxidative stress and enhanced inflammation were more predominant in AVs from male AS diabetic patients. Osteogenic markers were exclusively increased in the AVs of diabetic women. Basal characterization of VICs confirmed that oxidative stress, inflammation, calcification, and metabolic alteration profiles were increased in diabetic VICs with sex-specific differences. VICs cultured in hyperglycemic-like conditions triggered inflammatory responses in men, whereas in women rapid and higher production of pro-osteogenic molecules. CONCLUSIONS: DM produces sex-specific pathological phenotypes in AV of AS patients. Importantly, women with diabetes are more prone to develop AV calcification. DM should be considered as a risk factor in AS especially in women. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12933-023-02009-w. |
format | Online Article Text |
id | pubmed-10583330 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-105833302023-10-19 Influence of diabetes mellitus on the pathological profile of aortic stenosis: a sex-based approach Martín-Núñez, Ernesto Goñi-Olóriz, Miriam Matilla, Lara Garaikoetxea, Mattie Mourino-Alvarez, Laura Navarro, Adela Fernández-Celis, Amaya Tamayo, Ibai Gainza, Alicia Álvarez, Virginia Sádaba, Rafael Barderas, María G. Jover, Eva López-Andrés, Natalia Cardiovasc Diabetol Research BACKGROUND: Diabetes mellitus (DM) accelerates the progression of aortic stenosis (AS), but how their underlying molecular mechanisms interact is not clear. Moreover, whether DM contributes to clinically relevant sex-differences in AS is unknown. In this work we aim to characterize the sex-specific profile of major pathological mechanisms fundamental to aortic valve (AV) degeneration in AS patients with or without concomitant DM. METHODS: 283 patients with severe AS undergoing surgical valve replacement (27.6% DM, 59.4% men) were recruited. Expression of pathological markers related to AS were thoroughly assessed in AVs and valve interstitial cells (VICs) according to sex and presence of DM. Complementary in vitro experiments in VICs in the presence of high-glucose levels (25 mM) for 24, 48 and 72 h were performed. RESULTS: Oxidative stress and metabolic dysfunction markers were increased in AVs from diabetic AS patients compared to non-diabetic patients in both sexes. However, disbalanced oxidative stress and enhanced inflammation were more predominant in AVs from male AS diabetic patients. Osteogenic markers were exclusively increased in the AVs of diabetic women. Basal characterization of VICs confirmed that oxidative stress, inflammation, calcification, and metabolic alteration profiles were increased in diabetic VICs with sex-specific differences. VICs cultured in hyperglycemic-like conditions triggered inflammatory responses in men, whereas in women rapid and higher production of pro-osteogenic molecules. CONCLUSIONS: DM produces sex-specific pathological phenotypes in AV of AS patients. Importantly, women with diabetes are more prone to develop AV calcification. DM should be considered as a risk factor in AS especially in women. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12933-023-02009-w. BioMed Central 2023-10-17 /pmc/articles/PMC10583330/ /pubmed/37848892 http://dx.doi.org/10.1186/s12933-023-02009-w Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This 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 | Research Martín-Núñez, Ernesto Goñi-Olóriz, Miriam Matilla, Lara Garaikoetxea, Mattie Mourino-Alvarez, Laura Navarro, Adela Fernández-Celis, Amaya Tamayo, Ibai Gainza, Alicia Álvarez, Virginia Sádaba, Rafael Barderas, María G. Jover, Eva López-Andrés, Natalia Influence of diabetes mellitus on the pathological profile of aortic stenosis: a sex-based approach |
title | Influence of diabetes mellitus on the pathological profile of aortic stenosis: a sex-based approach |
title_full | Influence of diabetes mellitus on the pathological profile of aortic stenosis: a sex-based approach |
title_fullStr | Influence of diabetes mellitus on the pathological profile of aortic stenosis: a sex-based approach |
title_full_unstemmed | Influence of diabetes mellitus on the pathological profile of aortic stenosis: a sex-based approach |
title_short | Influence of diabetes mellitus on the pathological profile of aortic stenosis: a sex-based approach |
title_sort | influence of diabetes mellitus on the pathological profile of aortic stenosis: a sex-based approach |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10583330/ https://www.ncbi.nlm.nih.gov/pubmed/37848892 http://dx.doi.org/10.1186/s12933-023-02009-w |
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