Goñi Olóriz, Miriam

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https://academica-e.unavarra.es/handle/2454/53548

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Goñi Olóriz

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Miriam

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Ciencias de la Salud

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1355071

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813193

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2023 - 20252
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Author: Jover, Eva × Subject: Aortic stenosis ×

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Now showing 1 - 2 of 2
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    PublicationOpen Access
    Chemerin is a new sex-specific target in aortic stenosis concomitant with diabetes regulated by the aldosterone/mineralocorticoid receptor axis
    (American Physiological Society, 2025-01-20) Goñi Olóriz, Miriam; Garaikoetxea Zubillaga, Mattie; San Ildefonso-García, Susana; Fernández Celis, Amaya; Castillo, Paula; Navarro, Adela; Álvarez, Virginia ; Sádaba Sagredo, Rafael; Jover, Eva; Martín Núñez, Ernesto; López Andrés, Natalia; Ciencias de la Salud; Osasun Zientziak; Gobierno de Navarra / Nafarroako Gobernua
    Diabetes mellitus (DM) increases the risk of aortic stenosis (AS) and worsens its pathophysiology in a sex-specific manner. Aldosterone/mineralocorticoid receptor (Aldo/MR) pathway participates in the early stages of AS and in other diabetic-related cardiovascular complications. We aim to identify new sex-specific Aldo/MR targets in AS complicated with DM. We performed discovery studies using Olink Proteomics technology in 87 AS patient-derived aortic valves (AVs) (N ¼ 28 and N ¼ 19 nondiabetic and diabetic men; N ¼ 32 and N ¼ 8 nondiabetic and diabetic women, respectively) and human cytokine array (N ¼ 24 AVs/sex/condition). Both approaches revealed chemerin as a target differentially upregulated in AVs from male diabetic patients, further validated in a cohort of stenotic AVs (N ¼ 283, 27.6% DM, 59.4% men). Valvular chemerin levels are directly correlated with valve interstitial cell (VIC) activation, MR, inflammation, angiogenesis, and calcification markers exclusively in diabetic men. In vitro, Aldo (10-8 M) treatment exclusively increased chemerin levels in valve interstitial cells (VICs) from male patients with DM. Aldo also upregulated inflammatory, angiogenic, and osteogenic markers in DM and non-DM donors¿ VICs, which were prevented by MR antagonism. Increased glucose levels in cell media upregulated chemerin in VICs from male diabetic patients. Overall, RARRES2-knockdown in male diabetic VICs resulted in the downregulation of inflammatory, angiogenic, and osteogenic markers and blocked Aldo-induced responses in high glucose conditions. These data suggest the Aldo/MR pathway selectively increases chemerin in VICs from diabetic men, promoting inflammation, angiogenesis, and calcification associated with AS progression.
  • Thumbnail Image
    PublicationOpen Access
    Influence of diabetes mellitus on the pathological profile of aortic stenosis: a sex-based approach
    (Springer Nature, 2023) Martín Núñez, Ernesto; Goñi Olóriz, Miriam; Matilla Cuenca, Lara; Garaikoetxea Zubillaga, Mattie; Mourino-Álvarez, Laura; Navarro, Adela; Fernández Celis, Amaya; Tamayo Rodríguez, Ibai; Gaínza Calleja, Alicia; Álvarez, Virginia; Sádaba Sagredo, Rafael; Barderas, María G.; Jover, Eva; López Andrés, Natalia; Ciencias de la Salud; Osasun Zientziak
    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.