For Manuscript Submission, Check or Review Login please go to Submission Websites List.
For the academic login, please select your country in the dropdown list. You will be redirected to verify your credentials.
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