1,721,205 research outputs found
Inhibition of Galectin-3 Pathway Prevents Isoproterenol-Induced Left Ventricular Dysfunction and Fibrosis in Mice
No full textGalectin-3 and myocardial fibrosis in nonischemic dilated cardiomyopathy
No full textLeft ventricular (LV) fibrosis, assessed by late gadolinium enhancement (LGE) at cardiac magnetic resonance imaging (MRI), is a marker of LV remodeling, and holds prognostic value in nonischemic dilated cardiomyopathy (NICM). Galectin-3 has been shown to participate in tissue fibrogenesis and to be a prognosticator in heart failure. Our aim was to investigate the relationships between galectin-3 circulating level and myocardial fibrosis at MRI in patients with NICM
Baseline cardiovascular risk assessment in cancer patients scheduled to receive cardiotoxic cancer therapies: a position statement and new risk assessment tools from the C ardio‐ O ncology S tudy G roup of the H eart F ailure A ssociation of the E uropean S ociety of C ardiology in collaboration with the I nternational C ardio‐ O ncology S ociety
No full textRole of galectin-3 in cardiac dysfunction after acute kidney injury
No full textLe Syndrome Cardio-Rénal de type 3 (SCR-3) désigne une insuffisance cardiaque aiguë (ICA) secondaire à une agression rénale aiguë (ARA). La physiopathologie du SCR-3 est complexe et encore très mal comprise. L’objectif de ce travail de thèse est de mettre en évidence le rôle de la Galectine-3 (Gal-3), protéine impliquée dans l’inflammation, la fibrose et le remodelage cardiaque, dans un modèle murin de SCR-3. Préalablement aux travaux impliquant le rein, nous avons mis en évidence que Gal-3 était un effecteur clé du remodelage cardiaque en réponse à un stress aigu à l'isoprénaline (Vergaro et al., 2014). Dans un modèle murin d’ischémie/reperfusion rénale (IRR) avec néphrectomie du rein controlatéral nous avons montré que l’IRR induisait une dysfonction rénale transitoire (pic de créatinine et d’urée à 24h post-IRR et retour à la normale à 72h) et une élévation précoce (à 6h) de la quantité de cytokines pro-inflammatoires au niveau plasmatique. Au niveau cardiaque, on observait une augmentation de biomarqueurs d’agression (BNP et QSOX1-mRNAs) et d'inflammation (CD68, MCP1 et Galectin-3-ARNm) dans les 72h suivant l’opération. A un temps plus tardif, 28 jours, l’IR rénale induisait une inflammation et de la fibrose cardiaque et conduisait à une dysfonction cardiaque (-10% de la fraction de raccourcissement). Pour déterminer le rôle de Gal-3 dans ce modèle, des souris WT ont été traitées avec du MCP (Modified Citrus Pectin, un inhibiteur de Gal-3) avant (J-3) ou après (J+1) l’opération, et des souris KO Gal-3 ont également été utilisées. L’inhibition pharmacologique de Gal-3 (MCP) ou génétique prévenait l’augmentation plasmatique des cytokines pro-inflammatoires, l’apparition de la fibrose et de la dysfonction cardiaques à J28 post-IRR. Dans le but de valider les résultats obtenus dans ce premier modèle et de dissocier les effets cardiaques de la dysfonction rénale nous avons effectué les mêmes analyses dans un autre modèle d’agression rénale qui n’induit pas de dysfonction rénale. Ce modèle consiste en une occlusion unilatérale de l’uretère (UUO). Les résultats obtenus confirment le modèle d’agression rénale, avec l’apparition à J28 post-UUO d’une fibrose et d’une dysfonction cardiaques. Gal-3 semblait tout autant impliquée que dans le premier modèle car son inhibition par le MCP prévenait les dommages cardiaques. Par la suite, des souris WT et KO Gal-3 ont été soumises à une greffe de moelle osseuse. Les souris WT ont été greffées avec de la moelle osseuse (BM) de KO et inversement (WTKO BM et KOWT BM). Les souris chimères ainsi obtenues n’exprimaient pas (WTKO BM) ou exprimaient (KOWT BM) Gal-3 uniquement dans les cellules issues de la moelle osseuse. Ces résultats montrent que chez les WTKO BM, avec une délétion de Gal-3 spécifique des cellules issues de la moelle osseuse, l’IRR n’induisait ni fibrose ni dysfonction cardiaque à J28. L’ensemble des résultats met en évidence l’apparition d’une agression cardiaque aiguë en réponse à une agression rénale qui conduit sur le long terme à une dysfonction cardiaque, prévenues chez les souris KO Gal-3 ou les WT traitées au MCP. Ces résultats montrent que la Galectine-3, et spécifiquement la Gal-3 provenant des cellules de la moelle osseuse (probablement les macrophages), a un rôle clé dans les dommages cardiaques après agression rénale.The type 3 Cardio-Renal Syndrome (CRS-3) refers to an Acute Heart Failure (AHF) secondary to an Acute Kidney Injury (AKI). The pathophysiology of CRS-3 is complex and still poorly understood. The aim of this thesis is to highlight the role of Galectin-3 (Gal-3), a protein involved in inflammation, fibrosis and cardiac remodeling, in a mouse model of CRS-3.Prior to work involving the kidney, we found that Gal-3 was a key effector of cardiac remodeling in response to acute isoprenaline stress (Vergaro et al., 2014).In a murine model of renal ischemia/reperfusion (RIR) with contralateral nephrectomy we have shown that RIR induces transient renal dysfunction (peak of creatinine and urea at 24 hours post-RIR and return to normal at 72h) and an early rise (at 6h) in the amount of plasmatic pro-inflammatory cytokines. At the cardiac level, there was an increase in biomarkers of aggression (BNP and QSOX1-mRNAs) and inflammation (CD68, MCP1 and Galectin-3-mRNA) in the 72 hours following the surgery. At a later time, 28 days, renal IR induced inflammation and cardiac fibrosis and led to cardiac dysfunction (-10% of the shortening fraction). To determine the role of Gal-3 in this model, WT mice were treated with MCP (Modified Citrus Pectin, a Gal-3 inhibitor) before (J-3) or after (J+1) surgery, and Gal-3 KO mice were also used. The pharmacological inhibition of Gal-3 (MCP) or genetic, prevented the increase of plasmatic pro-inflammatory cytokines, the onset of cardiac fibrosis and cardiac dysfunction at day 28 post-RIR. In order to validate results obtained in the first model and to dissociate the cardiac effects of renal dysfunction, we performed the same analyzes in another model of renal injury that does not induce renal dysfunction. This model consists of an unilateral ureteral occlusion (UUO). The results obtained confirm the model of CRS-3, with the appearance at D28 post-UUO of cardiac fibrosis and dysfunction. Gal-3 seemed as equally involved as in the first model because its inhibition by MCP prevented heart damage.Subsequently, WT and Gal-3 KO mice were subjected to bone marrow transplantation. The WT mice were grafted with Gal-3 KO bone marrow (BM) and vice versa (WTKO BM and KOWT BM). The chimeric mice obtained did not express (WTKO BM) or express (KOWT BM) Gal-3 only in bone marrow-derived cells. These results show that in WTKO BM, with a specific Gal-3 deletion in bone marrow-derived cells, RIR did not induce fibrosis or cardiac dysfunction at D28.The overall results highlight the emergence of acute cardiac injury in response to an acute kidney injury leading at long term to cardiac dysfunction. These effects are prevented in Gal-3 KO mice or MCP treated mice. These results show that Galectin-3, and specifically Gal-3 from bone marrow derived-cells (probably macrophages), has a key role in cardiac damage after renal aggression
Galectin-3 in heart failure with preserved ejection fraction
No full text<p>In the last decades it has been appreciated that many patients with heart failure (HF) suffer from HF with preserved ejection fraction (HFpEF). The diagnosis and treatment of HFpEF is difficult, as we lack specific markers of the disease and no specific treatments have been identified. Galectin-3 has a strong relationship to several aspects of the pathophysiology of HF, especially myocardial fibrosis, the transition from compensated to decompensated HF, and co-morbidities such as renal disease and diabetes. Many of these traits are very commonly observed in patients with HFpEF, and this suggests that galectin-3 may be particularly important and useful in the study of HFpEF. This review summarizes our knowledge of the role of galectin-3 in fibrosis, specifically in experimental models of HF and HFpEF. Galectin-3 may be a marker and also a causal factor, and experimental studies suggested that galectin-3 may be a target for therapy in HFpEF. The detrimental effects of aldosterone may, in part, be conferred via galectin-3, and there are data to suggest that aldosterone blockers are of more benefit in patients with high levels of galectin-3. Furthermore, the relationship of galectin-3 to clinical correlates of developing HFpEF in human subjects is discussed, and the association between increased levels of galectin-3 and new-onset HF and mortality in the general population is highlighted. Additionally, the usefulness of galectin-3 in patients with established HFpEF is described. We conclude that galectin-3 may be useful for early detection, phenotyping, risk stratification, and therapeutic targeting of individuals with early or established HFpEF in which fibrosis is a major contributor to the disease. Finally, we propose areas of further research that should validate the role of galectin-3 in HFpEF.</p>
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
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