Examinando por Autor "Aravena, Cristobal"

Mostrando 1 - 2 de 2
  • Miniatura
    Ítem
    Disseminated intravascular coagulation phenotype is regulated by the TRPM7 channel during sepsis
    (2023-12) Jiménez‑Dinamarca, Ivanka; Prado, Yolanda; Tapia, Pablo; Gatica, Sebastian; Alt, Clemens; P. Lin, Charles; Martínez, Cristian Reyes; G. Feijóo, Carmen; Aravena, Cristobal; González‑Canace, Alejandra; Correa, Simón; Varela, Diego; Cabello‑Verrugio, Claudio; Simon, Felipe
    Background: Sepsis is an uncontrolled inflammatory response against a systemic infection that results in elevated mortality, mainly induced by bacterial products known as endotoxins, producing endotoxemia. Disseminated intravascular coagulation (DIC) is frequently observed in septic patients and is associated with organ failure and death. Sepsis activates endothelial cells (ECs), promoting a prothrombotic phenotype contributing to DIC. Ion channel-mediated calcium permeability participates in coagulation. The transient reception potential melastatin 7 (TRPM7) non-selective divalent cation channel that also contains an α-kinase domain, which is permeable to divalent cations including Ca2+, regulates endotoxin-stimulated calcium permeability in ECs and is associated with increased mortality in septic patients. However, whether endothelial TRPM7 mediates endotoxemia-induced coagulation is not known. Therefore, our aim was to examine if TRPM7 mediates coagulation during endotoxemia. Results: The results showed that TRPM7 regulated endotoxin-induced platelet and neutrophil adhesion to ECs, dependent on the TRPM7 ion channel activity and by the α-kinase function. Endotoxic animals showed that TRPM7 mediated neutrophil rolling on blood vessels and intravascular coagulation. TRPM7 mediated the increased expression of the adhesion proteins, von Willebrand factor (vWF), intercellular adhesion molecule 1 (ICAM-1), and P-selectin, which were also mediated by the TRPM7 α-kinase function. Notably, endotoxin-induced expression of vWF, ICAM-1 and P-selectin were required for endotoxin-induced platelet and neutrophil adhesion to ECs. Endotoxemic rats showed increased endothelial TRPM7 expression associated with a procoagulant phenotype, liver and kidney dysfunction, increased death events and an increased relative risk of death. Interestingly, circulating ECs (CECs) from septic shock patients (SSPs) showed increased TRPM7 expression associated with increased DIC scores and decreased survival times. Additionally, SSPs with a high expression of TRPM7 in CECs showed increased mortality and relative risk of death. Notably, CECs from SSPs showed significant results from the AUROC analyses for predicting mortality in SSPs that were better than the Acute Physiology and Chronic Health Evaluation II (APACHE II) and the Sequential Organ Failure Assessment (SOFA) scores. Conclusions: Our study demonstrates that sepsis-induced DIC is mediated by TRPM7 in ECs. TRPM7 ion channel activity and α-kinase function are required by DIC-mediated sepsis-induced organ dysfunction and its expression are associated with increased mortality during sepsis. TRPM7 appears as a new prognostic biomarker to predict mortality associated to DIC in SSPs, and as a novel target for drug development against DIC during infectious inflammatory diseases. © 2023, The Author(s).
  • No hay miniatura disponible
    Ítem
    From genes to systems: The role of food supplementation in the regulation of sepsis-induced inflammation
    (Elsevier B.V., 2024-01) Prado, Yolanda; Aravena, Diego; Gatica, Sebastian; Llancalahuen, Felipe M.; Aravena, Cristobal; Gutiérrez-Vera, Cristián; Carreño, Leandro J.; Cabello-Verrugio, Claudio; Simon, Felipe
    Systemic inflammation includes a widespread immune response to a harmful stimulus that results in extensive systemic damage. One common example of systemic inflammation is sepsis, which is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Under the pro-inflammatory environment of sepsis, oxidative stress contributes to tissue damage due to dysfunctional microcirculation that progressively causes the failure of multiple organs that ultimately triggers death. To address the underlying inflammatory condition in critically ill patients, progress has been made to assess the beneficial effects of dietary supplements, which include polyphenols, amino acids, fatty acids, vitamins, and minerals that are recognized for their immuno-modulating, anticoagulating, and analgesic properties. Therefore, we aimed to review and discuss the contribution of food-derived supplementation in the regulation of inflammation from gene expression to physiological responses and summarize the precedented potential of current therapeutic approaches during systemic inflammation. © 2023