| Content Provider |
World Health Organization (WHO)-Global Index Medicus |
| Author |
Esfahani, Hrag Horckmans, Michael Di Pietrantonio, Larissa Boeynaems, Jean-Marie Balligand, Jean-Luc Dessy, Chantal Clouet, Sophie Communi, Didier Robaye, Bernard Beauloye, Christophe |
| Description |
Author Affiliation: Horckmans M ( Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire, Université Libre de Bruxelles, 1070 Brussels, Belgium); Esfahani H ( Unité de Pharmacologie et de Thérapeutique, Université Catholique de Louvain, 1200 Brussels, Belgium); Beauloye C ( Pôle de Recherche Cardiovasculaire, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, 1200 Brussels, Belgium); Clouet S ( Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire, Université Libre de Bruxelles, 1070 Brussels, Belgium); di Pietrantonio L ( Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire, Université Libre de Bruxelles, 1070 Brussels, Belgium); Robaye B ( Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire, Université Libre de Bruxelles, 6041 Gosselies, Belgium); Balligand JL ( Unité de Pharmacologie et de Thérapeutique, Université Catholique de Louvain, 1200 Brussels, Belgium); Boeynaems JM ( Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire, Université Libre de Bruxelles, 1070 Brussels, Belgium); Dessy C ( Unité de Pharmacologie et de Thérapeutique, Université Catholique de Louvain, 1200 Brussels, Belgium); Communi D ( Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire, Université Libre de Bruxelles, 1070 Brussels, Belgium) |
| Abstract |
Nucleotides are released in the heart under pathological conditions, but little is known about their contribution to cardiac inflammation. The present study defines the P2Y4 nucleotide receptor, expressed on cardiac microvascular endothelial cells and involved in postnatal heart development, as an important regulator of the inflammatory response to cardiac ischemia. P2Y4-null mice displayed smaller infarcts in the left descending artery ligation model, as well as reduced neutrophil infiltration and fibrosis. Gene profiling identified inter alia endothelin-1 (ET-1) as one of the target genes of P2Y4 in ischemic heart. The reduced level of ET-1 was correlated with reduction of microvascular hyperpermeability, neutrophil infiltration, and endothelial adhesion molecule expression, and it could be explained by the decreased number of endothelial cells in P2Y4-null mice. Expression analysis of metalloproteinases and their tissue inhibitors in ischemic heart revealed reduced expression of matrix metalloproteinase (MMP)-9, reported to be potentially regulated by ET-1, and MMP-8, considered as neutrophil collagenase, as well as reduction of tissue inhibitor of MMP-1 and tissue inhibitor of MMP-4 in P2Y4-null mice. Reduction of cardiac permeability and neutrophil infiltration was also observed in P2Y4-null mice in LPS-induced inflammation model. Protection against infarction resulting from loss of P2Y4 brings new therapeutic perspectives for cardiac ischemia and remodeling. |
| ISSN |
00221767 |
| e-ISSN |
15506606 |
| Journal |
The Journal of Immunology |
| Issue Number |
4 |
| Volume Number |
194 |
| Language |
English |
| Publisher |
The American Association of Immunologists |
| Publisher Date |
2015-02-15 |
| Publisher Place |
United States |
| Access Restriction |
Open |
| Subject Keyword |
Endothelin-1 Biosynthesis Myocardial Infarction Metabolism Pathology Receptors, Purinergic P2 Deficiency Animals Disease Models, Animal Down-regulation Enzyme-linked Immunosorbent Assay Immunohistochemistry Mice Mice, Knockout Physiopathology Real-time Polymerase Chain Reaction Transcriptome Research Support, Non-u.s. Gov't Discipline Immunology |
| Content Type |
Text |
| Resource Type |
Article |
| Subject |
Immunology and Allergy Immunology |
