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Proteomic and Biological Analysis of an In Vitro Human Endothelial System in Response to Drug Anaphylaxis

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Yuste-Montalvo, Alma & Fernandez Bravo, Sergio & Oliva, Tamara & Pastor Vargas, Carlos & Betancor, Diana & Goikoetxea, María José & Laguna Martínez, Jose Julio & López, Juan Antonio & Alvarez Llamas, Gloria & Cuesta Herranz, Javier & Martin Lorenzo, Marta & Esteban, Vanesa .Proteomic and Biological Analysis of an In Vitro Human Endothelial System in Response to Drug Anaphylaxis.

ISO 690

Yuste-Montalvo, Alma & Fernandez Bravo, Sergio & Oliva, Tamara & Pastor Vargas, Carlos & Betancor, Diana & Goikoetxea, María José & Laguna Martínez, Jose Julio & López, Juan Antonio & Alvarez Llamas, Gloria & Cuesta Herranz, Javier & Martin Lorenzo, Marta & Esteban, Vanesa. Proteomic and Biological Analysis of an In Vitro Human Endothelial System in Response to Drug Anaphylaxis.

https://hdl.handle.net/20.500.12080/25238
dc.contributor.author Yuste-Montalvo, Alma
dc.contributor.author Fernandez Bravo, Sergio
dc.contributor.author Oliva, Tamara
dc.contributor.author Pastor Vargas, Carlos
dc.contributor.author Betancor, Diana
dc.contributor.author Goikoetxea, María José
dc.contributor.author Laguna Martínez, Jose Julio
dc.contributor.author López, Juan Antonio
dc.contributor.author Alvarez Llamas, Gloria
dc.contributor.author Cuesta Herranz, Javier
dc.contributor.author Martin Lorenzo, Marta
dc.contributor.author Esteban, Vanesa
dc.date.accessioned 2021-07-27T09:15:44Z
dc.date.available 2021-07-27T09:15:44Z
dc.date.created 2021-06-25
dc.identifier.uri https://hdl.handle.net/20.500.12080/25238
dc.description.abstract Anaphylaxis is a life-threatening systemic hypersensitivity reaction. During anaphylaxis, mediator release by effector cells causes endothelial barrier breakdown, increasing vascular permeability and leakage of fluids, which may lead to tissue edema. Although endothelial cells (ECs) are key players in this context, scant attention has been paid to the molecular analysis of the vascular system, and further analyses of this cell type are necessary, especially in humans. The protein expression pattern of human microvascular ECs was analyzed in response to sera from anaphylactic patients (EC-anaphylaxis) and sera from non-allergic subjects (EC-control) after 2 hours of contact. Firstly, a differential quantitative proteomic analysis of the protein extracts was performed by mass spectrometry using an isobaric labeling method. Second, the coordinated behavior of the identified proteins was analyzed using systems biology analysis (SBA). The proteome of the EC-anaphylaxis system showed 7,707 proteins, of which 1,069 were found to be significantly altered between the EC-control and EC-anaphylaxis groups (p-value < 0.05). Among them, a subproteome of 47 proteins presented a high rate of change (|DZq| ¿ 3). This panel offers an endothelial snapshot of the anaphylactic reaction. Those proteins with the highest individual changes in abundance were hemoglobin subunits and structural support proteins. The interacting network analysis of this altered subproteome revealed that the coagulation and complement systems are the main biological processes altered in the EC-anaphylactic system. The comprehensive SBA resulted in 5,512 functional subcategories (biological processes), 57 of which were significantly altered between EC-control and EC-anaphylaxis. The complement system, once again, was observed as the main process altered in the EC system created with serum from anaphylactic patients. Findings of the current study further our understanding of the underlying pathophysiological mechanisms operating in anaphylactic reactions. New target proteins and relevant signaling pathways operating in the in vitro endothelial-serum system have been identified. Interestingly, our results offer a protein overview of the micro-EC-anaphylaxis environment. The relevance of the coagulation, fibrinolytic, contact and complement systems in human anaphylaxis is described. Additionally, the untargeted high-throughput analysis used here is a novel approach that reveals new pathways in the study of the endothelial niche in anaphylaxis. Keywords: endothelium, anaphylaxis, proteomics, coagulation and complement systems, drug allergy, system biological analysis es_ES
dc.format application/acad es_ES
dc.language eng es_ES
dc.rights CC-BY es_ES
dc.rights.uri http://creativecommons.org/licenses/by/4.0/deed.es es_ES
dc.title Proteomic and Biological Analysis of an In Vitro Human Endothelial System in Response to Drug Anaphylaxis es_ES
dc.type info:eu-repo/semantics/article es_ES
dc.rights.accessrights info:eu-repo/semantics/openAccess es_ES
dc.identifier.location N/A es_ES


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