VEGF-C induced angiogenesis preferentially occurs at a distance from lymphangiogenesis.
OBJECTIVE
Vascular endothelial growth factor-C (VEGF-C) has been shown to stimulate both angiogenesis and lymphangiogenesis in some but not all models where VEGF-C is over-expressed. Our aim was to investigate the interaction between lymphangiogenesis and angiogenesis in adult tissues regulated by VEGF-C and identify evidence of polarized growth of lymphatics driven by specialized cells at the tip of the growing sprout.


RESULTS
We used an adult model of lymphangiogenesis in the rat mesentery. The angiogenic effect of VEGF-C was markedly attenuated in the presence of a growing lymphatic network. Furthermore, we show that this growth of lymphatic vessels can occur both by recruitment of isolated lymphatic islands to a connected network and by filopodial sprouting. The latter is independent of polarized tip cell differentiation that can be generated all along lymphatic capillaries, independently of the proliferation status of the lymphatic endothelial cells.


CONCLUSIONS
These results both demonstrate a dependence of VEGF-C-mediated angiogenesis on lymphatic vascular networks and indicate that the mechanism of VEGF-C-mediated lymphangiogenesis is different from that of classical angiogenic mechanisms.
Microvascular Research Laboratories, Department of Physiology, University of Bristol, BS2 8EJ Bristol, UK.
Andrew V
AV
Benest
Steven J
SJ
Harper
Seppo Yla
SY
Herttuala
Kari
K
Alitalo
David O
DO
Bates
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D004729:Endothelium, Lymphatic / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins / Q000378:metabolism; D042583:Lymphangiogenesis; D042601:Lymphatic Vessels / Q000378:metabolism*; D008297:Male; D008643:Mesentery / Q000098:blood supply*; D018715:Microscopy, Video; D018919:Neovascularization, Physiologic; D010641:Phenotype; D011554:Pseudopodia / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013997:Time Factors; D042582:Vascular Endothelial Growth Factor C / Q000235:genetics / Q000378:metabolism*
D011993:Recombinant Fusion Proteins; D042582:Vascular Endothelial Growth Factor C; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins