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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Author: Garaikoetxea Zubillaga, Mattie × Subject: Extracellular matrix ×

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    PublicationOpen Access
    The presence of adipose tissue in aortic valves influences inflammation and extracellular matrix composition in chronic aortic regurgitation
    (MDPI, 2025-03-28) Sádaba, Alba; Garaikoetxea Zubillaga, Mattie; Tiraplegui, Carolina; San Ildefonso-García, Susana; Goñi Olóriz, Miriam; Fernández Celis, Amaya; Martín Núñez, Ernesto; Castillo, Paula; Álvarez, Virginia; Sádaba Sagredo, Rafael; Jover, Eva; Navarro, Adela; López Andrés, Natalia; Ciencias de la Salud; Osasun Zientziak
    Adipose tissue is present in aortic valves (AVs). Valve interstitial cells (VICs) could differentiate into adipogenic lineages. We here characterize whether the presence of adipose tissue in the AV influences inflammation and extracellular matrix (ECM) composition in patients with aortic regurgitation (AR). A total of 144 AVs were analyzed by histological and molecular techniques. We performed discovery studies using Olink Proteomics® technology in 40 AVs (N = 16 without and N = 24 with adipose tissue). In vitro, human white adipocytes (HWAs) or VICs were cultured with adipogenic media and co-cultured with control VICs. Of Avs, 67% presented white-like adipocytes within the spongiosa. Discovery studies revealed increased levels of inflammatory and ECM molecules in AVs containing adipocytes. Interestingly, the presence of adipocytes was associated with greater AV thickness, higher inflammation, and ECM remodeling, which was characterized by increased proinflammatory molecules, collagen, fibronectin, proteoglycans, and metalloproteinases. AV thickness positively correlated with markers of adipose tissue, inflammation, and ECM. In vitro, adipocyte-like VICs expressed higher levels of adipocyte markers, increased cytokines, fibronectin, decorin, and MMP-13. Analyses of supernatants from co-cultured control VICs with HWA or adipocyte-like VICs showed higher expression of inflammatory mediators, collagen type I, proteoglycans, and metalloproteinases. AVs presenting adipocytes were thicker and exhibited changes characterized by increased inflammation accompanied by aberrant expression of collagen, proteoglycans, and metalloproteinases. VICs could differentiate into adipogenic pathway, affect neighbor VICs, and contribute to inflammation, collagen and proteoglycan accumulation, as well as to metalloproteinases secretion. In summary, the presence of adipose tissue in AV could modify its composition, favoring inflammation and remodeling with an impact on AV thickness.
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    PublicationOpen Access
    Sex differences in aortic valve inflammation and remodeling in chronic severe aortic regurgitation
    (American Physiological Society, 2025-03-01) Tiraplegui, Carolina; Garaikoetxea Zubillaga, Mattie; Sádaba, Alba ; San Ildefonso-García, Susana; Goñi Olóriz, Miriam; Fernández Celis, Amaya; Martín Núñez, Ernesto; Álvarez, Virginia; Sádaba Sagredo, Rafael; Anand, Vidhu; Jover, Eva; Navarro, Adela; López Andrés, Natalia; Ciencias de la Salud; Osasun Zientziak; Gobierno de Navarra / Nafarroako Gobernua
    Aortic regurgitation (AR) is more prevalent in males, although cellular and molecular mechanisms underlying the sex differences in prevalence and pathophysiology are unknown. This study evaluates the impact of sex on aortic valve (AV) inflammation and remodeling and the cellular differences in valvular interstitial cells (VICs) and valvular endothelial cells (VECs) in patients with AR. A total of 144 patients (27.5% female) with severe chronic AR were included. AVs were analyzed by imaging, histological, and molecular biology techniques (ELISA, RT-PCR). VICs and VECs isolated from patients with AR were characterized and further treated with transforming growth factor (TGF)-β. Anatomically, male had smaller index aortic dimensions and greater AV thickness. Proteome profiler analyzes in AVs (n = 40/sex) evidenced higher expression of inflammatory markers in male and that was further validated (interleukins, chemokines). Histological composition showed higher expression of inflammatory mediators and collagen thick fibers in AVs from male. Male VICs and VECs secreted higher levels of inflammatory markers than female cells. Interestingly, male VICs produced higher amounts of collagen type I and lower fibronectin and aggrecan, whereas male VECs secreted lower decorin. TGF-β exclusively enhanced inflammation in male VICs and decorin and aggrecan in female VICs. Compared with male, AVs from female were thinner, less inflamed, and fibrotic. VICs seem to be the key cell type responsible for the sex-differences. Valvular inflammation associated with an active remodeling process could be a key pathophysiological process involved in AR.