Vascular endothelial growth factor increases the migration and proliferation of smooth muscle cells through the mediation of growth factors released by endothelial cells.
BACKGROUND
Vascular endothelial growth factor (VEGF), a highly specific chemotactic and mitogenic factor for vascular endothelial cells (EC), appears to be involved in the development of atherosclerosis. The purpose of our study was to assess if VEGF might indirectly stimulate SMC migration and proliferation in a EC-SMC coculture system, through the mediation of growth factors released by EC.


METHODS
Bovine aortic SMC were cocultured with bovine aortic EC treated with hrVEGF, to assess SMC proliferation and migration. The release and mRNA expression of basic fibroblast growth factor (bFGF) and transforming growth factor beta(1) (TGFbeta(1)) were assessed by ELISA and PCR analysis.


RESULTS
hrVEGF (10 ng/ml), added to EC cocultured with SMC, induced a significant increase in tritiated thymidine uptake by SMC as compared to controls (P < 0.01) and a significant increase in SMC migration in respect to control (27%; P < 0.01). EC stimulated with hrVEGF increased the release and the expression of bFGF and decreased the release and the expression of TGFbeta(1) with a statistically significant difference in respect to controls (P < 0.001).


CONCLUSIONS
VEGF indirectly stimulates SMC proliferation and migration through the modulation of bFGF and TGFbeta(1) released by EC.
Cucina
Alessandra
A
Department of Surgery Pietro Valdoni-University of Rome La Sapienza, Via A. Scarpa 14, 00161, Rome, Italy. alessandra.cucina@uniromal.it
Borrelli
Valeria
V
Randone
Bruto
B
Coluccia
Pierpaolo
P
Sapienza
Paolo
P
Cavallaro
Antonino
A
D000818:Animals; D001013:Aorta, Thoracic; D002417:Cattle; D002455:Cell Division / Q000187:drug effects*; D002465:Cell Movement / Q000187:drug effects*; D018920:Coculture Techniques; D017077:Culture Media, Conditioned; D016228:Endothelial Growth Factors / Q000494:pharmacology* / Q000502:physiology; D004730:Endothelium, Vascular / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000378:metabolism; D006133:Growth Substances / Q000378:metabolism*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology* / Q000502:physiology; D008222:Lymphokines / Q000494:pharmacology* / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D011994:Recombinant Proteins / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D053773:Transforming Growth Factor beta1; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D017077:Culture Media, Conditioned; D016228:Endothelial Growth Factors; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D012333:RNA, Messenger; D011994:Recombinant Proteins; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D016222:Fibroblast Growth Factor 2