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    Examinando por Autor "Maldonado-Agurto, Rodrigo"

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      Seasonal transcriptome profile across three different tissues of the Andean Killifish Orestias ascotanensis
      (Springer Nature, 2025-06-10) Maldonado-Agurto, Rodrigo; Acevedo, Elvis; Maracaja-Coutinho, Vinicius; Montecino, Martin
      The Andean killifish Orestias ascotanensis inhabits the high-altitude Ascotán Salt Pan, an environment with variable salinity, high UV exposure, low oxygen, and extreme daily temperature fluctuations. These conditions make it an excellent model for studying high-altitude fish biology. However, the transcriptomic responses of O. ascotanensis to seasonal acclimation remain unexplored. To investigate seasonal and tissue-specific transcriptomic profiles, RNA-seq was performed on 42 libraries from gills, skin, and muscle tissues of 14 individuals collected in summer (n = 7) and winter (n = 7). Each library had a median of 105 million reads. Principal component analysis revealed strong tissue-specific expression, and seasonal differential expression analyses identified significant transcriptomic changes within each tissue. Additionally, a bioinformatics pipeline identified 10,365 high-confidence long non-coding RNAs (lncRNAs), predicted by at least three computational tools. Compared to protein-coding genes, lncRNAs exhibited higher tissue specificity, with a predominance of monoexonic structures and shorter exon lengths. This dataset provides the first comprehensive view of seasonal mRNA and lncRNA expression in O. ascotanensis tissues.
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      The role of cellular senescence in endothelial dysfunction and vascular remodelling in arteriovenous fistula maturation
      (Wiley, 2025-02-20) González, Ignacia; Maldonado-Agurto, Rodrigo
      Haemodialysis (HD) is often required for patients with end-stage renal disease. Arteriovenous fistulas (AVFs), a surgical procedure connecting an artery to a vein, are the preferred vascular access for HD due to their durability and lower complication rates. The aim of AVFs is to promote vein remodelling to accommodate increased blood flow needed for dialysis. However, many AVFs fail to mature properly, making them unsuitable for dialysis. Successful maturation requires remodelling, resulting in an increased luminal diameter and thickened walls to support the increased blood flow. After AVF creation, haemodynamic changes due to increased blood flow on the venous side of the AVF initiate a cascade of events that, when successful, lead to the proper maturation of the AVF, making it suitable for cannulation. In this process, endothelial cells play a crucial role since they are in direct contact with the frictional forces exerted by the blood, known as shear stress. Patients requiring HD often have other conditions that increase the burden of senescent cells, such as ageing, diabetes and hypertension. These senescent cells are characterized by irreversible growth arrest and the secretion of pro-inflammatory and pro-thrombotic factors, collectively known as the senescence-associated secretory phenotype (SASP). This accumulation can impair vascular function by promoting inflammation, reducing vasodilatation, and increasing thrombosis risk, thus hindering proper AVF maturation and function. This review explores the contribution of senescent endothelial cells to AVF maturation and explores potential therapeutic strategies to alleviate the effects of senescent cell accumulation, aiming to improve AVF maturation rates.
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      Transcriptional activation of genes associated with the matrisome is a common feature of senescent endothelial cells
      (Springer Nature, 2025-02-13) Gonzalez, Ignacia; Arredondo, Sebastián; Maldonado-Agurto, Rodrigo
      Cellular senescence is a stable cell cycle arrest that occurs in response to various stress stimuli and affects multiple cell types, including endothelial cells (ECs). Senescent cells accumulate with age, and their removal has been linked to reduced age-related diseases. However, some senescent cells are important for tissue homeostasis. Therefore, understanding the diversity of senescent cells in a cell-type-specific manner and their underlying molecular mechanisms is essential. Senescence impairs key ECs functions which are necessary for vascular homeostasis, leading to endothelial dysfunction and age-related vascular diseases. In order to gain insights into these mechanisms, we analyzed publicly available RNA-seq datasets to identify gene expression changes in senescent ECs induced by doxorubicin, irradiation, and replication exhaustion. While only a few genes were consistently differentially expressed across all conditions, some gene ontologies (GO) were shared. Among these, our analysis focused on validating the expression of genes associated with the matrisome, which includes genes encoding for extracellular matrix (ECM) structural components and ECM-associated proteins, in a doxorubicin-induced senescence model. Our results show that the matrisome transcriptome undergoes significant remodeling in senescent endothelial cells, regardless of the specific inducers of senescence, highlighting the importance of understanding how ECM alterations affect senescence.
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