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Cardiovascular Research Advance Access originally published online on December 7, 2007
Cardiovascular Research 2008 78(2):315-323; doi:10.1093/cvr/cvm094
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Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2007. For permissions please email: journals.permissions@oxfordjournals.org
The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that the original authorship is properly and fully attributed; the Journal, Learned Society and Oxford University Press are attributed as the original place of publication with correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions@oxfordjournals.org.

VEGF-C induced angiogenesis preferentially occurs at a distance from lymphangiogenesis

Andrew V. Benest1,{dagger}, Steven J. Harper1, Seppo Yla Herttuala2, Kari Alitalo3 and David O. Bates1,*

1 Microvascular Research Laboratories, Department of Physiology, University of Bristol, BS2 8EJ Bristol, UK
2 Department of Biotechnology and Molecular Medicine, A.I. Virtanen Institute for Molecular Sciences, University of Kuopio, Kuopio, Finland
3 Molecular/Cancer Biology Laboratory, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland

*Corresponding author. +44 117 928 9818; fax: +44 117 928 8151. E-mail address: Dave.Bates{at}bris.ac.uk

Aims: 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.

Methods and 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.

Conclusion: 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.

KEYWORDS Angiogenesis; Lymphangiogenesis; VEGF-C; Sprouting

Time for primary review: 23 days

{dagger} Present address. Division of Vascular Oncology and Metastasis A190, DKFZ, Im Neuenheimer Feld 581 (TP4), D-69120 Heidelberg, Germany.


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