Influence of diabetes mellitus on the pathological profile of aortic stenosis: a sex-based approach

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dc.contributor.authorMartín Núñez, Ernesto
dc.contributor.authorGoñi Olóriz, Miriam
dc.contributor.authorMatilla Cuenca, Lara
dc.contributor.authorGaraikoetxea Zubillaga, Mattie
dc.contributor.authorMourino-Álvarez, Laura
dc.contributor.authorNavarro, Adela
dc.contributor.authorFernández Celis, Amaya
dc.contributor.authorTamayo Rodríguez, Ibai
dc.contributor.authorGaínza Calleja, Alicia
dc.contributor.authorÁlvarez, Virginia
dc.contributor.authorSádaba Sagredo, Rafael
dc.contributor.authorBarderas, María G.
dc.contributor.authorJover, Eva
dc.contributor.authorLópez Andrés, Natalia
dc.contributor.departmentCiencias de la Saludes_ES
dc.contributor.departmentOsasun Zientziakeu
dc.date.accessioned2024-04-26T10:30:32Z
dc.date.available2024-04-26T10:30:32Z
dc.date.issued2023
dc.date.updated2024-04-26T10:00:40Z
dc.description.abstractBackground: 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.es_ES
dc.description.sponsorshipThis work was supported by a Miguel Servet contract (CP13/00221) and Fondo de Investigaciones Sanitarias (PI21/00280) from the Instituto de Salud Carlos III – FEDER, as well as by Gobierno de Navarra (GºNa 01/21). EMN was supported by a Margarita Salas postdoctoral fellowship (ULL-MS-P14, granted by Universidad de la Laguna and Ministerio de Universidades - Orden UNI/551/2021 de 26 de mayo and Fondos Next Generation EU), MG was supported by a Miguel Servet Foundation Ph.D. studentship, LM was supported by a PFIS Ph.D. studentship (FI19/00302) and EJ was supported by a Sara Borrell postdoctoral fellowship (CD19/00251). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Open Access funding provided by Universidad Pública de Navarra.es_ES
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dc.identifier.citationMartín-Núñez, E., Goñi-Olóriz, M., Matilla, L., Garaikoetxea, M., Mourino-Alvarez, L., Navarro, A., Fernández-Celis, A., Tamayo, I., Gainza, A., Álvarez, V., Sádaba, R., Barderas, M. G., Jover, E., López-Andrés, N. (2023) Influence of diabetes mellitus on the pathological profile of aortic stenosis: a sex-based approach. Cardiovascular Diabetology, 22(280), 1-15. https://doi.org/10.1186/s12933-023-02009-w.es_ES
dc.identifier.doi10.1186/s12933-023-02009-w
dc.identifier.issn1475-2840
dc.identifier.urihttps://academica-e.unavarra.es/handle/2454/48039
dc.language.isoengen
dc.publisherSpringer Natureen
dc.relation.ispartofCardiovascular Diabetology (2023), vol. 22, núm. 280es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/MINECO//CP13%2F00221/ES/
dc.relation.projectIDinfo:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 (ISCIII)/PI21%2F00280/ES/
dc.relation.projectIDinfo:eu-repo/grantAgreement/Gobierno de Navarra//01%2F21/
dc.relation.publisherversionhttps://doi.org/10.1186/s12933-023-02009-w
dc.rights© The Author(s) 2023. This article is licensed under a Creative Commons Attribution 4.0 International License.en
dc.rights.accessRightsinfo:eu-repo/semantics/openAccess
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectAortic stenosisen
dc.subjectAortic valve diseaseen
dc.subjectHeart valve diseaseen
dc.subjectSex-differenceen
dc.subjectType 2 diabetesen
dc.titleInfluence of diabetes mellitus on the pathological profile of aortic stenosis: a sex-based approachen
dc.typeinfo:eu-repo/semantics/article
dc.type.versioninfo:eu-repo/semantics/publishedVersion
dspace.entity.typePublication
relation.isAuthorOfPublication919e6260-466a-40a4-aded-bfbf1549d7b8
relation.isAuthorOfPublication803d8f90-85aa-4e9f-bfa0-30454dc4e7dd
relation.isAuthorOfPublication488f1d4a-17fc-4f8c-87c0-8939257c87d7
relation.isAuthorOfPublication23d03177-1c69-4293-bfd4-1de28bf3c05b
relation.isAuthorOfPublication.latestForDiscovery803d8f90-85aa-4e9f-bfa0-30454dc4e7dd

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