Annexin A2-Mediated Plasminogen Activation in Endothelial Cells Contributes to the Proangiogenic Effect of Adenosine A2A Receptors
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 contribu...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-04-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2021.654104/full |
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| author | María D. Valls María Soldado Jorge Arasa Jorge Arasa Miguel Perez-Aso Adrienne J. Williams Bruce N. Cronstein Bruce N. Cronstein Bruce N. Cronstein M. Antonia Noguera M. Antonia Noguera M. Carmen Terencio M. Carmen Terencio M. Carmen Montesinos M. Carmen Montesinos |
| author_facet | María D. Valls María Soldado Jorge Arasa Jorge Arasa Miguel Perez-Aso Adrienne J. Williams Bruce N. Cronstein Bruce N. Cronstein Bruce N. Cronstein M. Antonia Noguera M. Antonia Noguera M. Carmen Terencio M. Carmen Terencio M. Carmen Montesinos M. Carmen Montesinos |
| author_sort | María D. Valls |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-21T17:35:30Z |
| format | Article |
| id | doaj.art-c8d2f273ff4446ee99617da77018caa8 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-21T17:35:30Z |
| publishDate | 2021-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-c8d2f273ff4446ee99617da77018caa82022-12-21T18:55:46ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122021-04-011210.3389/fphar.2021.654104654104Annexin A2-Mediated Plasminogen Activation in Endothelial Cells Contributes to the Proangiogenic Effect of Adenosine A2A ReceptorsMaría D. Valls0María Soldado1Jorge Arasa2Jorge Arasa3Miguel Perez-Aso4Adrienne J. Williams5Bruce N. Cronstein6Bruce N. Cronstein7Bruce N. Cronstein8M. Antonia Noguera9M. Antonia Noguera10M. Carmen Terencio11M. Carmen Terencio12M. Carmen Montesinos13M. Carmen Montesinos14Departament of Pharmacology, Faculty of Pharmacy, Universitat de València, Valencia, SpainDepartament of Pharmacology, Faculty of Pharmacy, Universitat de València, Valencia, SpainDepartament of Pharmacology, Faculty of Pharmacy, Universitat de València, Valencia, SpainInstituto Interuniversitario de Investigación de Reconocimiento Molecular y Desarrollo Tecnológico (IDM), Universitat Politècnica de València, Universitat de València, Valencia, SpainDivision of Translational Medicine, Department of Medicine, NYU School of Medicine, New York, NY, United StatesDivision of Translational Medicine, Department of Medicine, NYU School of Medicine, New York, NY, United StatesDivision of Translational Medicine, Department of Medicine, NYU School of Medicine, New York, NY, United StatesDivision of Rheumatology, Department of Medicine, NYU School of Medicine, New York, NY, United StatesMedical Science Building, NYU Langone Health, New York, NY, United StatesDepartament of Pharmacology, Faculty of Pharmacy, Universitat de València, Valencia, SpainInstituto Universitario de Biotecnología y Biomedicina (BIOTECMED) Universitat de València, Valencia, SpainDepartament of Pharmacology, Faculty of Pharmacy, Universitat de València, Valencia, SpainInstituto Interuniversitario de Investigación de Reconocimiento Molecular y Desarrollo Tecnológico (IDM), Universitat Politècnica de València, Universitat de València, Valencia, SpainDepartament of Pharmacology, Faculty of Pharmacy, Universitat de València, Valencia, SpainInstituto Interuniversitario de Investigación de Reconocimiento Molecular y Desarrollo Tecnológico (IDM), Universitat Politècnica de València, Universitat de València, Valencia, SpainAdenosine 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.https://www.frontiersin.org/articles/10.3389/fphar.2021.654104/fullannexin A2microvascular endothelial cellsplasminogen activator inhibitor-1tissue plasminogen activatorurokinase plasminogen activatoradenosine receptors |
| spellingShingle | María D. Valls María Soldado Jorge Arasa Jorge Arasa Miguel Perez-Aso Adrienne J. Williams Bruce N. Cronstein Bruce N. Cronstein Bruce N. Cronstein M. Antonia Noguera M. Antonia Noguera M. Carmen Terencio M. Carmen Terencio M. Carmen Montesinos M. Carmen Montesinos Annexin A2-Mediated Plasminogen Activation in Endothelial Cells Contributes to the Proangiogenic Effect of Adenosine A2A Receptors Frontiers in Pharmacology annexin A2 microvascular endothelial cells plasminogen activator inhibitor-1 tissue plasminogen activator urokinase plasminogen activator adenosine receptors |
| title | Annexin A2-Mediated Plasminogen Activation in Endothelial Cells Contributes to the Proangiogenic Effect of Adenosine A2A Receptors |
| title_full | Annexin A2-Mediated Plasminogen Activation in Endothelial Cells Contributes to the Proangiogenic Effect of Adenosine A2A Receptors |
| title_fullStr | Annexin A2-Mediated Plasminogen Activation in Endothelial Cells Contributes to the Proangiogenic Effect of Adenosine A2A Receptors |
| title_full_unstemmed | Annexin A2-Mediated Plasminogen Activation in Endothelial Cells Contributes to the Proangiogenic Effect of Adenosine A2A Receptors |
| title_short | Annexin A2-Mediated Plasminogen Activation in Endothelial Cells Contributes to the Proangiogenic Effect of Adenosine A2A Receptors |
| title_sort | annexin a2 mediated plasminogen activation in endothelial cells contributes to the proangiogenic effect of adenosine a2a receptors |
| topic | annexin A2 microvascular endothelial cells plasminogen activator inhibitor-1 tissue plasminogen activator urokinase plasminogen activator adenosine receptors |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2021.654104/full |
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