Examinando por Autor "Nus, Meritxell"

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NR4A1 Deletion in Marginal Zone B Cells Exacerbates Atherosclerosis in Mice.
(American Heart Association Journals, 2020-11) Nus, Meritxell; Basatemur, Gemma; Galán, María; Cros-Brunsó, Laia; Zhao, Tian X; Masters, Leanne; Harrison, James; Figg, Nichola; Tsiantoulas, Dimitrios; Geissmann, Frederic; Binder, Christoph J; Sage, Andrew P; Mallat, Ziad
Objective: NR4A orphan receptors have been well studied in vascular and myeloid cells where they play important roles in the regulation of inflammation in atherosclerosis. NR4A1 (nerve growth factor IB) is among the most highly induced transcription factors in B cells following BCR (B-cell receptor) stimulation. Given that B cells substantially contribute to the development of atherosclerosis, we examined whether NR4A1 regulates B-cell function during atherogenesis. Approach and Results: We found that feeding Ldlr-/- mice a Western diet substantially increased Nr4a1 expression in marginal zone B (MZB) cells compared with follicular B cells. We then generated Ldlr-/- mice with complete B- or specific MZB-cell deletion of Nr4a1. Complete B-cell deletion of Nr4a1 led to increased atherosclerosis, which was accompanied by increased T follicular helper cell-germinal center axis response, as well as increased serum total cholesterol and triglycerides levels. Interestingly, specific MZB-cell deletion of Nr4a1 increased atherosclerosis in association with an increased T follicular helper-germinal center response but without any impact on serum cholesterol or triglyceride levels. Nr4a1-/- MZB cells showed decreased PDL1 (programmed death ligand-1) expression, which may have contributed to the enhanced T follicular helper response. Conclusions: Our findings reveal a previously unsuspected role for NR4A1 in the atheroprotective role of MZB cells.
Oxidative Stress and Inflammatory Markers in Abdominal Aortic Aneurysm.
(MDPI, 2021-04-14) Sánchez-Infantes, David; Nus, Meritxell; Navas-Madroñal, Miquel; Pérez, Belén; Barros-Membrilla, Antonio José; Soto, Begoña; Martínez-González, José; Camacho, Mercedes; Rodriguez, Cristina; Mallat, Ziad; Galán, María
Abdominal aortic aneurysm (AAA) is increasing due to aging of the population and is a major cause of death among the elderly. Ultrasound screening programs are useful in early diagnosis, but aneurysm size is not always a good predictor of rupture. Our aim was to analyze the value of circulating molecules related to oxidative stress and inflammation as new biomarkers to assist the management of AAA. The markers were quantified by ELISA, and their expression in the aneurysmal wall was studied by real-time PCR and by immunostaining. Correlation analysis of the studied markers with aneurysm diameter and peak wall stress (PWS), obtained by finite element analysis, and multivariate regression analysis to assess potential confounding factors were performed. Our study shows an extensive inflammatory infiltration in the aneurysmal wall, mainly composed by T-cells, macrophages and B-cells and altered levels of reactive oxygen species (ROS), IgM, IgG, CD38, GDF15, S100A4 and CD36 in plasma and in the aneurysmal tissue of AAA patients compared with controls. Circulating levels of IgG, CD38 and GDF15 positively correlated with abdominal aortic diameter, and CD38 was correlated with PWS. Our data show that altered levels of IgG, CD38 and GDF15 have potential diagnostic value in the assessment of AAA.