Human Apo-Lactoferrin Enhances Angiogenesis Mediated by Vascular Endothelial Growth Factor A in vivoNorrby K.
Department of Pathology, Institute of Laboratory Medicine, Sahlgrenska Academy, Göteborg University, Gothenburg, Sweden
Background: Lactoferrin, LF, a multifunctional iron- and heparin-binding protein, present in exocrine body secretions and leukocytes, is remarkably resistant to proteolysis. Ingested bovine iron-unsaturated LF, apo-bLF, suppresses VEGF-A-mediated angiogenesis in a previously described rat mesentery angiogenesis assay, possibly explaining, at least in part, its established anticancer effect in rats and mice. Methods: Using the same experimental system, we have now studied the effect of (i) ingested human apo-LF, apo-hLF, on angiogenesis mediated by VEGF-A and bFGF, (ii) ingested human iron-saturated LF, holo-hLF, on VEGF-A-mediated angiogenesis and (iii) subcutaneous continuously infused apo-hLF on VEGF-A-mediated angiogenesis. Results: Ingested holo-hLF did not affect VEGF-A-mediated angiogenesis. Ingested apo-hLF (from one and the same batch) significantly enhanced VEGF-A-mediated angiogenesis but did not affect bFGF-mediated angiogenesis. Moreover, subcutaneously infused apo-hLF also significantly stimulated VEGF-A-mediated angiogenesis. Conclusion: Taken together, the data suggest that apo-hLF exerts a specific proangiogenic effect in VEGF-A-mediated angiogenesis. Clearly, human and bovine apo-LF exert opposite effects on VEGF-A-induced angiogenesis. Differences in molecular features between human and bovine LFs of possible significance for the outcome are discussed. In hypoxia, compensatory collateral circulation is mediated primarily by VEGF-A. We hypothesize that systemically administered apo-hLF may promote collateral blood vessel formation at hypoxic sites in normal tissue, thus counteracting ischemia and infarction.
© 2004 S. Karger AG, Basel
Dr. Klas Norrby
Department of Pathology, Göteborg University
Sahlgrenska University Hospital
SE–413 45 Gothenburg (Sweden)
Tel. +46 31 342 19 54, Fax +46 31 82 71 94, E-Mail firstname.lastname@example.org
The study was supported by grants from the Swedish Medical Research Council, project No. 5249.
Received: November 21, 2003
Accepted after revision: April 5, 2004
Published online: June 10, 2004
Number of Print Pages : 12
Number of Figures : 2, Number of Tables : 5, Number of References : 102
Journal of Vascular Research (Incorporating International Journal of Microcirculation)
Founded 1964 as Angiologica by M. Comèl and L. Laszt (1964–1973) continued as Blood Vessels by J.A. Bevan (1974–1991)
Official Journal of the European Society for Microcirculation
Vol. 41, No. 4, Year 2004 (Cover Date: July-August 2004)
Journal Editor: U. Pohl, Munich
ISSN: 1018–1172 (print), 1423–0135 (Online)
For additional information: http://www.karger.com/jvr