OBJECTIVES: This study sought to examine the role of platelet-derived growth factor (PDGF) signaling in healing myocardial infarcts. BACKGROUND: Platelet-derived growth factor isoforms exert potent fibrogenic effects through interactions with PDGF receptor (PDGFR)-alpha and PDGFR-beta. In addition, PDGFR-beta signaling mediates coating of developing vessels with mural cells, leading to the formation of a mature vasculature. We hypothesized that PDGFR activation may regulate fibrosis and vascular maturation in healing myocardial infarcts. METHODS: Mice undergoing reperfused infarction protocols were injected daily with a neutralizing anti-PDGFR-beta antibody (APB5), an anti-PDGFR-alpha antibody (APA5), or control immunoglobulin G, and were killed after 7 days of reperfusion. RESULTS: The PDGF-B, PDGFR-alpha, and PDGFR-beta mRNA expression was induced in reperfused mouse infarcts. Perivascular cells expressing phosphorylated PDGFR-beta were identified in the infarct after 7 days of reperfusion, indicating activation of the PDGF-BB/PDGFR-beta pathway. The PDGFR-beta blockade resulted in impaired maturation of the infarct vasculature, enhanced capillary density, and formation of dilated uncoated vessels. Defective vascular maturation in antibody-treated mice was associated with increased and prolonged extravasation of red blood cells and monocyte/macrophages, suggesting increased permeability. These defects resulted in decreased collagen content in the healing infarct. In contrast, PDGFR-alpha inhibition did not affect vascular maturation, but significantly decreased collagen deposition in the infarct. CONCLUSIONS: Platelet-derived growth factor signaling critically regulates postinfarction repair. Both PDGFR-beta- and PDGFR-alpha-mediated pathways promote collagen deposition in the infarct. Activation of PDGF-B/PDGFR-beta is also involved in recruitment of mural cells by neovessels, regulating maturation of the infarct vasculature. Acquisition of a mural coat and maturation of the vasculature promotes resolution of inflammation and stabilization of the scar.
OBJECTIVES: This study sought to examine the role of platelet-derived growth factor (PDGF) signaling in healing myocardial infarcts. BACKGROUND: Platelet-derived growth factor isoforms exert potent fibrogenic effects through interactions with PDGF receptor (PDGFR)-alpha and PDGFR-beta. In addition, PDGFR-beta signaling mediates coating of developing vessels with mural cells, leading to the formation of a mature vasculature. We hypothesized that PDGFR activation may regulate fibrosis and vascular maturation in healing myocardial infarcts. METHODS:Mice undergoing reperfused infarction protocols were injected daily with a neutralizing anti-PDGFR-beta antibody (APB5), an anti-PDGFR-alpha antibody (APA5), or control immunoglobulin G, and were killed after 7 days of reperfusion. RESULTS: The PDGF-B, PDGFR-alpha, and PDGFR-beta mRNA expression was induced in reperfused mouseinfarcts. Perivascular cells expressing phosphorylated PDGFR-beta were identified in the infarct after 7 days of reperfusion, indicating activation of the PDGF-BB/PDGFR-beta pathway. The PDGFR-beta blockade resulted in impaired maturation of the infarct vasculature, enhanced capillary density, and formation of dilated uncoated vessels. Defective vascular maturation in antibody-treated mice was associated with increased and prolonged extravasation of red blood cells and monocyte/macrophages, suggesting increased permeability. These defects resulted in decreased collagen content in the healing infarct. In contrast, PDGFR-alpha inhibition did not affect vascular maturation, but significantly decreased collagen deposition in the infarct. CONCLUSIONS: Platelet-derived growth factor signaling critically regulates postinfarction repair. Both PDGFR-beta- and PDGFR-alpha-mediated pathways promote collagen deposition in the infarct. Activation of PDGF-B/PDGFR-beta is also involved in recruitment of mural cells by neovessels, regulating maturation of the infarct vasculature. Acquisition of a mural coat and maturation of the vasculature promotes resolution of inflammation and stabilization of the scar.
Authors: Sven Schneider; Philipp Kloimstein; Johannes Pammer; Werner Brannath; Matthaeus Ch Grasl; Boban M Erovic Journal: Eur Arch Otorhinolaryngol Date: 2013-10-04 Impact factor: 2.503
Authors: Marcin Bujak; Hyuk Jung Kweon; Khaled Chatila; Na Li; George Taffet; Nikolaos G Frangogiannis Journal: J Am Coll Cardiol Date: 2008-04-08 Impact factor: 24.094