Cardiovascular Research Advance Access [Accepted Manuscript] published online on December 7, 2007
Cardiovascular Research, doi:10.1093/cvr/cvm094
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VEGF-C induced angiogenesis preferentially occurs at a distance from lymphangiogenesis
1 Microvascular Research Laboratories, Department of Physiology, University of Bristol, BS2 8EJ, UK
2 A.I. Virtanen Institute for Molecular Sciences Department of Biotechnology and Molecular Medicine, University of Kuopio, Finland
3 Molecular/Cancer Biology Laboratory, Biomedicum Helsinki, University Of Helsinki Finland
Corresponding Author: Dr David Bates Microvascular Research Laboratories, Department of Physiology, University of Bristol, BS2 8EJ, UK TEL 0117 928 9818, Fax 0117 928 9818, email: Dave.Bates{at}bris.ac.uk
AIM: 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 polarised growth of lymphatics driven by specialised cells at the tip of the growing sprout.
METHODS: We used an adult model of lymphangiogenesis in the rat mesentery.
RESULTS: The angiogenic effect of VEGF-C was markedly attenuated in the presence of a growing lymphatic network. Further, 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 polarised 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.
KEYWORDS Angiogenesis; Lymphangiogenesis; VEGF-C
Time for primary review: 23
AV Benest Current address. Division of Vascular Oncology and Metastasis A190, DKFZ, Im Nuenheimer Feld 581 (TP4), D-69120 Heidelberg, Germany
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