Journal Article

Endothelial Progenitor Cells Induce a Phenotype Shift in Differentiated Endothelial Cells towards PDGF/PDGFRβ Axis-Mediated Angiogenesis

Wyler von Ballmoos, Moritz, Kalka, Christoph, Baumgartner, Iris, Yang, Zijiang, Völzmann, Jan, Di Santo, Stefano

2010

Overview

Endothelial Progenitor Cells (EPC) support neovascularization and regeneration of injured endothelium both by providing a proliferative cell pool capable of differentiation into mature vascular endothelial cells and by secretion of angiogenic growth factors. The aim of this study was to investigate the role of PDGF-BB and PDGFRβ in EPC-mediated angiogenesis of differentiated endothelial cells. Conditioned medium from human EPC (EPC-CM) cultured in hypoxic conditions contained substantially higher levels of PDGF-BB as compared to normoxic conditions (P<0.01). EPC-CM increased proliferation (1.39-fold; P<0.001) and migration (2.13-fold; P<0.001) of isolated human umbilical vein endothelial cells (HUVEC), as well as sprouting of vascular structures from ex vivo cultured aortic rings (2.78-fold increase; P = 0.01). The capacity of EPC-CM to modulate the PDGFRβ expression in HUVEC was assessed by western blot and RT-PCR. All the pro-angiogenic effects of EPC-CM on HUVEC could be partially inhibited by inactivation of PDGFRβ (P<0.01). EPC-CM triggered a distinct up-regulation of PDGFRβ (2.5±0.5; P<0.05) and its phosphorylation (3.6±0.6; P<0.05) in HUVEC. This was not observed after exposure of HUVEC to recombinant human PDGF-BB alone. These data indicate that EPC-CM sensitize endothelial cells and induce a pro-angiogenic phenotype including the up-regulation of PDGFRβ, thereby turning the PDGF/PDGFRβ signaling-axis into a critical element of EPC-induced endothelial angiogenesis. This finding may be utilized to enhance EPC-based therapy of ischemic tissue in future.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Angiogenesis / Animals / Aorta / Aorta - physiology / Blood platelets / Blotting, Western / Cardiovascular Disorders / Cardiovascular Disorders/Coronary Artery Disease / Cardiovascular Disorders/Peripheral Vascular Disease / Cardiovascular Disorders/Vascular Biology / Cell culture / Cell Differentiation / Cell migration / Cells (biology) / Cells, Cultured / Conditioning / Culture Media, Conditioned - metabolism / Culture Media, Conditioned - pharmacology / Cytokines / Deactivation / Endothelial cells / Endothelial Cells - cytology / Endothelial Cells - drug effects / Endothelial Cells - metabolism / Endothelium / Growth factors / Hospitals / Humans / Hypoxia / In Vitro Techniques / Inactivation / Insulin-like growth factors / Ischemia / Medicine / Metastasis / Neovascularization, Physiologic - drug effects / Neovascularization, Physiologic - physiology / Phosphorylation / Platelet-derived growth factor / Platelet-Derived Growth Factor - genetics / Platelet-Derived Growth Factor - metabolism / Platelet-Derived Growth Factor - pharmacology / Platelet-derived growth factor BB / Polymerase chain reaction / Proto-Oncogene Proteins c-sis / Rats / Rats, Wistar / Receptor, Platelet-Derived Growth Factor beta - genetics / Receptor, Platelet-Derived Growth Factor beta - metabolism / Recombinant Proteins - pharmacology / Regeneration / Reverse Transcriptase Polymerase Chain Reaction / Secretion / Signal Transduction - drug effects / Signal Transduction - physiology / Signaling / Stem cells / Stem Cells - cytology / Stem Cells - drug effects / Stem Cells - metabolism / Studies / Umbilical vein / Vascularization