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Annexin A2-Mediated Plasminogen Activation in Endothelial Cells Contributes to the Proangiogenic Effect of Adenosine A2A Receptors

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Annexin A2-Mediated Plasminogen Activation in Endothelial Cells Contributes to the Proangiogenic Effect of Adenosine A2A Receptors

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dc.contributor.author Valls, María D.
dc.contributor.author Soldado, María
dc.contributor.author Arasa Aparici, Jorge
dc.contributor.author Perez-Aso, Miguel
dc.contributor.author Williams, Adrienne J.
dc.contributor.author Cronstein, Bruce
dc.contributor.author Noguera Romero, María Antonia
dc.contributor.author Terencio Silvestre, María Carmen
dc.contributor.author Montesinos Mezquita, María Carmen
dc.date.accessioned 2021-07-26T13:32:30Z
dc.date.available 2021-07-26T13:32:30Z
dc.date.issued 2021
dc.identifier.citation Valls, María D. Soldado, María Arasa Aparici, Jorge Perez-Aso, Miguel Williams, Adrienne J. Cronstein, Bruce Noguera Romero, María Antonia Terencio Silvestre, María Carmen Montesinos Mezquita, Mª Carmen 2021 Annexin A2-Mediated Plasminogen Activation in Endothelial Cells Contributes to the Proangiogenic Effect of Adenosine A2A Receptors Frontiers In Pharmacology 12 654104
dc.identifier.uri https://hdl.handle.net/10550/80037
dc.description.abstract Adenosine A2A receptor mediates the promotion of wound healing and revascularization of injured tissue, in healthy and animals with impaired wound healing, through a mechanism depending upon tissue plasminogen activator (tPA), a component of the fibrinolytic system. In order to evaluate the contribution of plasmin generation in the proangiogenic effect of adenosine A2A receptor activation, we determined the expression and secretion of t-PA, urokinase plasminogen activator (uPA), plasminogen activator inhibitor-1 (PAI-1) and annexin A2 by human dermal microvascular endothelial cells stimulated by the selective agonist CGS-21680. The plasmin generation was assayed through an enzymatic assay and the proangiogenic effect was studied using an endothelial tube formation assay in Matrigel. Adenosine A2A receptor activation in endothelial cells diminished the release of PAI-1 and promoted the production of annexin A2, which acts as a cell membrane co-receptor for plasminogen and its activator tPA. Annexin A2 mediated the increased cell membrane-associated plasmin generation in adenosine A2A receptor agonist treated human dermal microvascular endothelial cells and is required for tube formation in an in vitro model of angiogenesis. These results suggest a novel mechanism by which adenosine A2A receptor activation promotes angiogenesis: increased endothelial expression of annexin A2, which, in turn, promotes fibrinolysis by binding tPA and plasminogen to the cell surface.
dc.language.iso eng
dc.relation.ispartof Frontiers In Pharmacology, 2021, vol. 12, num. 654104
dc.subject Farmacologia
dc.subject Vasodilatadors
dc.subject Proteïnes
dc.title Annexin A2-Mediated Plasminogen Activation in Endothelial Cells Contributes to the Proangiogenic Effect of Adenosine A2A Receptors
dc.type journal article es_ES
dc.date.updated 2021-07-26T13:32:31Z
dc.identifier.doi 10.3389/fphar.2021.654104
dc.identifier.idgrec 147464
dc.rights.accessRights open access es_ES

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