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(Circulation Research. 2007;100:1402.)
© 2007 American Heart Association, Inc.

Editorials

Silky, Sticky Chimeras-Designer VEGFs Display Their Wares

Michael Simons

From the Angiogenesis Research Center, Section of Cardiology, Departments of Medicine and Pharmacology and Toxicology, Dartmouth Medical School, Dartmouth-Hitchcock Medical Center, Lebanon, NH.

Correspondence to Michael Simons, MD, Section of Cardiology, DHMC, One Medical Center Drive, Lebanon, NH 03756. Phone: E-mail michael.simons@dartmouth.edu

See related articles, pages 1460–1467 and 1468–1475

Key Words: angiogenesis • growth factors • lymphatics • VEGF

An extract of the first 250 words of the full text is provided, because this article has no abstract.

To the casual observer of the VEGF field, the panoply of players involved already looks sufficiently intimidating; 5 VEGF genes (A,B,C,D and E) with multiple splicing variants encoding proteins of varied functionality, 3 high-affinity tyrosine kinase receptors (VEGF-R1, 2 and 3), and at least 2 nontyrosine kinase receptors (neuropilin-1 and 2). One would imagine that with such a variety we would have encountered by now all possible variations on the theme of VEGF control of new vessel growth, arterial or lymphatic. But one would be wrong. Two reports in this issue of Circulation Research by Kari Alitalo and colleagues demonstrate how various VEGF domains dictate hitherto unappreciated biological nuances of vascular growth and how these can be combined into "designer" VEGFs with new activities not present in parent molecules.^1,2

Principal VEGF-A domains include a signal peptide sequence, a VEGF homology domain (VHD) common to all VEGF but dictating specific VEGF receptor binding properties (VEGF-R1 and VEGF-R² in the case of VEGF-A VHD), and a heparin binding domain (HBD) encoded by exons 6 and 7 in VEGF₁₈₉ or a shorter HBD encoded only by exon 7 in VEGF-A₁₆₅. Exon 7 also encodes a neurolin-1 binding domain present in both VEGF-A₁₆₅ and A₁₈₉ (Figure). Similarly, VEGF-C principal domains include the signal peptide domain and VEGF-C VHD (in this case dictating VEGF-R² and VEGF-R3 binding) flanked by N- and C-terminal domains that normally undergo proteolytic process to form the mature protein (Figure). The C-terminal domain of . . . [Full Text of this Article]

Related Article:

Enhanced Capillary Formation Stimulated by a Chimeric Vascular Endothelial Growth Factor/Vascular Endothelial Growth Factor-C Silk Domain Fusion Protein

Salla Keskitalo, Tuomas Tammela, Johannes Lyytikka, Terhi Karpanen, Michael Jeltsch, Johanna Markkanen, Seppo Yla-Herttuala, and Kari Alitalo
Circ. Res. 2007 100: 1460-1467. [Abstract] [Full Text] [PDF]