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Characterization of the sex-specific pattern of angiogenesis and lymphangiogenesis in aortic stenosis

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dc.contributor.authorMatilla Cuenca, Lara
dc.contributor.authorMartín Núñez, Ernesto
dc.contributor.authorGaraikoetxea Zubillaga, Mattie
dc.contributor.authorNavarro, Adela
dc.contributor.authorVico, Julieta Anabela
dc.contributor.authorArrieta Paniagua, Vanessa
dc.contributor.authorGarcía Peña, Amaia
dc.contributor.authorFernández Celis, Amaya
dc.contributor.authorGaínza Calleja, Alicia
dc.contributor.authorÁlvarez, Virginia
dc.contributor.authorSádaba Sagredo, Rafael
dc.contributor.authorLópez Andrés, Natalia
dc.contributor.authorJover, Eva
dc.contributor.departmentCiencias de la Saludes_ES
dc.contributor.departmentOsasun Zientziakeu
dc.date.accessioned2023-02-13T08:55:12Z
dc.date.available2023-02-13T08:55:12Z
dc.date.issued2022
dc.date.updated2023-02-13T08:19:14Z
dc.description.abstractObjective: We aim to analyze sex-related differences in angiogenesis and lymphangiogenesis in aortic valves (AVs) and valve interstitial cells (VICs) from aortic stenosis (AS) patients. Approach and Results: Totally 230 patients (59% men) with severe AS undergoing surgical valve replacement were recruited. The density of total neovessels was higher in AVs from men as compared to women. Both small and medium neovessels were more abundant in men's AVs. Accordingly, male AVs exhibited higher CD31 and VE-cadherin expressions. The levels of the pro-angiogenic markers, such as vascular endothelial growth factor (VEGF)-A, VEGF receptor (VEGFR)1, VEGFR2, insulin-like growth factor-binding protein-2 (IGFBP-2), interleukin (IL)-8, chemerin, and fibroblast growth factor (FGF)-7, were increased in AVs from men. Transforming growth factor-¿ expression was higher in male AVs. The expression of antiangiogenic molecules thrombospondin (Tsp)-1, endostatin, and CD36 was upregulated in male AVs, although the levels of Tsp-2, IL-4, IL-12p70, and chondromodulin-1 were similar between both sexes. The number of lymphatic vessels and the expression of the lymphangiogenic markers Lyve-1 and D2-40 was higher in men's AV as well as VEGF-C, VEGF-D, and VEGFR3. Multivariate analyses adjusted for confounders further validated the sex-dependent expression of these targets. VICs isolated from men's AVs secreted higher amounts of the pro-angiogenic factors, VEGF-A, VEGFR1, IGFBP-2, and FGF-7, as well as the pro-lymphangiogenic factors, VEGF-C, VEGF-D, and VEGFR3, than women without changes in antiangiogenic markers. Conclusion: Our data show that aberrant angiogenic and lymphangiogenic cues are over-represented in male AVs. Importantly, the VIC is a relevant source of multiple morphogens involved in angiogenesis and lymphangiogenesis likely endowing the AV of men with the predominant calcific AS phenotypes.en
dc.description.sponsorshipThis work was supported by a Miguel Servet contract (CP13/00221) and by Fondo de Investigaciones Sanitarias (PI18/01875; PI21/00280) from the Instituto de Salud Carlos III - FEDER. LM was supported by a PFIS Ph.D. studentship (FI19/00302). EJ was supported by a Sara Borrell postdoctoral fellowship (CD19/00251). EM-N was supported by a Margarita Salas postdoctoral fellowship (ULL-MS-P14). MG was supported by a Miguel Servet Foundation Ph.D. studentship.en
dc.format.mimetypeapplication/pdfen
dc.identifier.citationMatilla, L., Martín-Núñez, E., Garaikoetxea, M., Navarro, A., Vico, J. A., Arrieta, V., García-Peña, A., Fernández-Celis, A., Gainza, A., Álvarez, V., Sádaba, R., López-Andrés, N., & Jover, E. (2022). Characterization of the sex-specific pattern of angiogenesis and lymphangiogenesis in aortic stenosis. Frontiers in Cardiovascular Medicine, 9. https://www.frontiersin.org/articles/10.3389/fcvm.2022.971802en
dc.identifier.doi10.3389/fcvm.2022.971802
dc.identifier.issn2297-055X
dc.identifier.urihttps://academica-e.unavarra.es/handle/2454/44682
dc.language.isoengen
dc.publisherFrontiers Mediaen
dc.relation.ispartofFrontiers in Cardiovascular Medicine 2022 12,9:971802en
dc.relation.projectIDinfo:eu-repo/grantAgreement/MINECO//CP13%2F00221/ES/en
dc.relation.projectIDinfo:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016 (ISCIII)/PI18%2F01875/ES/en
dc.relation.projectIDinfo:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 (ISCIII)/PI21%2F00280/ES/en
dc.relation.projectIDinfo:eu-repo/grantAgreement/ISCIII//FI19%2F00302en
dc.relation.projectIDinfo:eu-repo/grantAgreement/ISCIII//CD19%2F00251en
dc.relation.publisherversionhttps://doi.org/10.3389/fcvm.2022.971802
dc.rights© 2022 Matilla, Martín-Núñez, Garaikoetxea, Navarro, Vico, Arrieta, García-Peña, Fernández-Celis, Gainza, Álvarez, Sádaba, López-Andrés and Jover. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY)en
dc.rights.accessRightsAcceso abierto / Sarbide irekiaes
dc.rights.accessRightsinfo:eu-repo/semantics/openAccessen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectAngiogenesisen
dc.subjectAortic stenosisen
dc.subjectLymphangiogenesisen
dc.subjectSexen
dc.subjectValve interstitial cellsen
dc.titleCharacterization of the sex-specific pattern of angiogenesis and lymphangiogenesis in aortic stenosisen
dc.typeArtículo / Artikuluaes
dc.typeinfo:eu-repo/semantics/articleen
dc.type.versionVersión publicada / Argitaratu den bertsioaes
dc.type.versioninfo:eu-repo/semantics/publishedVersionen
dspace.entity.typePublication
relation.isAuthorOfPublication803d8f90-85aa-4e9f-bfa0-30454dc4e7dd
relation.isAuthorOfPublication23d03177-1c69-4293-bfd4-1de28bf3c05b
relation.isAuthorOfPublication.latestForDiscovery803d8f90-85aa-4e9f-bfa0-30454dc4e7dd

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