VEGFR-1–Selective VEGF Homologue PlGF Is Arteriogenic
| Autor: | Wolfgang Schaper, Herbert A. Weich, Peter Carmeliet, Matthias Heil, Borja Fernandez, Sandra Martin, Joop van den Heuvel, Katja Issbrücker, Gershon Golomb, Frederic Pipp, Tibor Ziegelhoeffer, Matthias Clauss |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Vascular Endothelial Growth Factor A
Integrins medicine.medical_specialty Time Factors Physiology Angiogenesis Integrin Endothelial Growth Factors Pregnancy Proteins Monocytes Mice Viral Proteins chemistry.chemical_compound Internal medicine medicine Animals Humans Receptor Ligation Placenta Growth Factor Mice Knockout Lymphokines Vascular Endothelial Growth Factor Receptor-1 biology Vascular Endothelial Growth Factors Macrophages Monocyte Arteries Femoral Artery Endothelial stem cell Vascular endothelial growth factor Vascular endothelial growth factor A medicine.anatomical_structure Endocrinology chemistry biology.protein Intercellular Signaling Peptides and Proteins Rabbits Arteriogenesis Cardiology and Cardiovascular Medicine |
| Zdroj: | Circulation Research. 92:378-385 |
| ISSN: | 1524-4571 0009-7330 |
| DOI: | 10.1161/01.res.0000057997.77714.72 |
| Popis: | Two signaling receptors for vascular endothelial growth factor (VEGF) in the vasculature are known with not yet well-understood roles in collateral vessel growth (arteriogenesis). In this study, we examined the involvement of the two VEGF receptors in arteriogenesis. Therefore, we used the VEGF homologue placenta growth factor (PlGF), which only binds to VEGFR-1 and VEGF-E, which only recognizes VEGFR-2. These peptides were locally infused over 7 days after ligation of the femoral artery in the rabbit. Evaluation of collateral growth by determining collateral conductance and angiographic scores demonstrated that the VEGFR-1–specific PlGF contributed significantly more to arteriogenesis than the VEGFR-2 specific VEGF-E. The combination of VEGF-E and PlGF did not exceed the effect of PlGF alone, indicating that cooperation of the two VEGF receptors in endothelial cell signaling is not required for arteriogenesis. In an in vitro model of angiogenesis, VEGF and VEGF-E were comparably active, whereas PlGF displayed no activity when given alone and did not further increase the effects of VEGF or VEGF-E. However, PlGF was as potent as VEGF when monocyte activation was assessed by monitoring integrin surface expression. In addition, accumulation of activated monocytes/macrophages in the periphery of collateral vessels in PlGF-treated animals was observed. Furthermore, in monocyte-depleted animals, the ability of PlGF to enhance collateral growth in the rabbit model and to rescue impaired arteriogenesis in PlGF gene–deficient mice was abrogated. Together, these data indicate that the arteriogenic activity observed with the VEGFR-1–specific PlGF is caused by its monocyte-activating properties. |
| Databáze: | OpenAIRE |
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