Goñi Olóriz, Miriam

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Goñi Olóriz

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Miriam

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Ciencias de la Salud

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Now showing 1 - 2 of 2
  • 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.
  • PublicationOpen Access
    Novel protocol for the transcriptomic analysis of endothelial extracellular vesicles in atherosclerosis
    (Elsevier, 2024-09-12) Saenz-Pipaon, Goren; Cenarro, Ana; Zazpe, Jon; Goñi Olóriz, Miriam; Martínez-Aguilar, Esther; Machado, Florencio J.D.; Marchese, Francesco P.; Orbe, Josune; López Andrés, Natalia; Civeira, Fernando; Páramo, José A.; Lara-Astiaso, David; Roncal Mancho, Carmen; Ciencias de la Salud; Osasun Zientziak
    Introduction: Despite the key role of the endothelium in atherosclerosis, there are no direct techniques for its analysis. The study of extracellular vesicles of endothelial origin (EEVs), might lead to the identification of molecular signatures and early biomarkers of atherosclerosis. The aim of this work was to set up the methods for EEVs separation and transcriptomic analysis. Methods: We adapted an antibody-magnetic-bead based immunocapture protocol for plasma EEVs separation from control (G1), subclinical atherosclerosis (G2) and peripheral artery disease subjects (PAD) (G3), and modified an ultra-low input RNASeq method (n = 5/group). By bioinformatics analysis we compared the transcriptome of plasma EEVs with that of human aortic endothelial cells (TeloHAECs), and then, searched for differentially expressed genes (DEG) among EEVs of G1, G2 and G3. From those DEG, UCP2 was selected for further validation in plasma EVs (qPCR), and in vitro, in stimulated TeloHAECs (IL-1 beta, TNF alpha, oxLDL and hypoxia). Results: The RNASeq analysis of plasma EEVs rendered 1667 genes enriched in transcripts expressed by TeloHAECs (NES: 1.93, p adjust = 1.4(e-73)). One hundred seventy DEGs were identified between G2 vs G1, and 180 between G3 vs G1, of which 17 were similarly expressed in G2 and G3 vs control, including UCP2. IL-1 beta and TNF alpha (10 ng/mL, p < 0.05), hypoxia (1% O-2, p = 0.05) and oxLDL (100 mu g/mL, p = 0.055) reduced UCP2 expression in TeloHAECs. Conclusions: We set up a protocol for EEVs separation and sequencing that might be useful for the identification of early markers of endothelial dysfunction in atherosclerosis.