Crotalid venom vascular endothelial growth factors has preferential affinity for VEGFR-1

Yuh-Ling Chen; Inn-Ho Tsai; Tse-Ming Hong; Shu-Huei Tsai

doi:10.1160/TH04-09-0568

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2005; 93(02): 331-338
DOI: 10.1160/TH04-09-0568

Endothelium and Vascular Development

Schattauer GmbH

Crotalid venom vascular endothelial growth factors has preferential affinity for VEGFR-1

Characterization of Protobothrops mucrosquamatus venom VEGF

Yuh-Ling Chen

¹Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan

²Institute of Oral Medicine, National Cheng Kung University, Tainan, Taiwan

,

Inn-Ho Tsai

¹Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan

,

Tse-Ming Hong

³School of Pharmacy, National Taiwan University, Taipei, Taiwan

,

Shu-Huei Tsai

⁴Department of Orthopaedics and Traumatology, School of Medicine, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan

› Author Affiliations

Abstract

Summary

Pm-VEGF, a novel member ofVEGF family from the venom gland of Taiwan habu (Protobothrops mucrosquamatu), is a disulfidelinked homodimer with 119 amino acid residues. Recombinant fusion Pm-VEGF was expressed in Escherichia coli, purified and refolded. Surface plasmon resonance was used to determine its binding kinetics toVEGF-receptors (VEGFR). Relative to human VEGF₁₆₅, the binding affinity of Pm-VEGF to the VEGFR-1 was 1.7-fold higher while affinity to the VEGFR-2 was 17-fold lower. But it did not bind theVEGFR-3 or neuropilin-1. Pm-VEGF promoted the proliferation and tissue factor production of endothelial cells, the neovascularization in the chicken chorioallantoic membrane, and increased vascular permeability. It also stimulated tissue-factor production and human monocyte chemotaxis, in accord with its specificity for VEGFR-1. Structural comparison among VEGF-proteins from various viper venoms revealed that the two subfamilies of vipers (Crotalinae and Viperinae) have evolved with distinct receptor-specificities for VEGFR-1 and VEGFR-2, respectively. Discussion on structureactivity relationships of the VEGFs further provided insight into residues important for the receptor-binding and specificities.

Keywords

Snake venom VEGF - receptor specificity - vascular permeability - angiogenesis - monocyte chemotaxis

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References

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