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          Institute: MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut)     Collection: Publikationen des W. G. Kerckhoff-Instituts     Display Documents

ID: 199066.0, MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut) / Publikationen des W. G. Kerckhoff-Instituts
VEGFR-1-selective VEGF homologue PlGF is arteriogenic: evidence for a monocyte-mediated mechanism
Authors:Pipp, F.; Heil, M.; Issbrucker, K.; Ziegelhoeffer, T.; Martin, S.; van den Heuvel, J.; Weich, H.; Fernandez, B.; Golomb, G.; Carmeliet, P.; Schaper, W.; Clauss, M.
Date of Publication (YYYY-MM-DD):2003-03-07
Title of Journal:Circulation Research
Issue / Number:4
Start Page:378
End Page:385
Review Status:not specified
Audience:Not Specified
Abstract / Description: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.
Free Keywords:Animals
; Arteries/*drug effects/pathology/physiopathology
; Endothelial Growth Factors/pharmacology
; Femoral Artery/surgery
; Human
; Integrins/biosynthesis/drug effects
; Intercellular Signaling Peptides and Proteins/pharmacology
; Ligation
; Lymphokines/pharmacology
; Macrophages/cytology/drug effects/metabolism
; Mice
; Mice, Knockout
; Monocytes/cytology/drug effects/metabolism
; Pregnancy Proteins/genetics/metabolism/*pharmacology
; Rabbits
; Support, Non-U.S. Gov't
; Time Factors
; Vascular Endothelial Growth Factor A
; Vascular Endothelial Growth Factor Receptor-1/*metabolism
; Vascular Endothelial Growth Factors
; Viral Proteins/pharmacology
External Publication Status:published
Document Type:Article
Communicated by:N. N.
Affiliations:MPI für physiologische und klinische Forschung
Identifiers:URL:http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=... [ID No:1]
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