Peptides derived from type I thrombospondin repeat-containing proteins of the CCN family inhibit proliferation and migration of endothelial cells

Emmanouil D. Karagiannis, Aleksander S. Popel

Research output: Contribution to journalArticlepeer-review

Abstract

Angiogenesis, or neovascularization, is tightly orchestrated by endogenous regulators that promote or inhibit the process. The fine-tuning of these pro- and anti-angiogenic elements (the angiogenic balance) helps establish the homeostasis in tissues, and any aberration leads to pathologic conditions. The type I thrombospondin repeats are a family of protein structural elements involved in the control of angiogenesis, and some proteins containing these repeats have been identified as negative regulators of angiogenesis. Here we identify a set of 11 novel, anti-angiogenic 18-20-amino acid peptides that are derived from proteins that belong to the CCN protein family and contain type I thrombospondin motifs. We have named these peptides spondinstatin-1, cyrostatin, connectostatin, nephroblastostatin, wispostatin-2, wispostatin-3, netrinstatin-5C, netrinstatin-5D, adamtsostatin-like-4, fibulostatin-6.1, and complestatin-C6 to reflect their origin. We have shown that these peptides inhibit proliferation and migration of human umbilical vein endothelial cells in vitro. By conducting a clustering analysis of the amino acid sequences using sequence similarity criteria and of the experimental results using a hierarchical clustering algorithm, we have demonstrated that there is an underlying correlation between the sequence and activity of the identified peptides. This combination of experimental and computational approaches introduces a novel systematic framework for studying peptide activity, identifying novel peptides with anti-angiogenic activity, and designing mimetic peptides with tailored properties.

Original languageEnglish (US)
Pages (from-to)2314-2323
Number of pages10
JournalInternational Journal of Biochemistry and Cell Biology
Volume39
Issue number12
DOIs
StatePublished - 2007

Keywords

  • Adamtsostatin-like-4
  • Angiogenesis
  • Complestatin-C6
  • Connectostatin
  • Cyrostatin
  • Endogenous
  • Endothelial cell
  • Fibulostatin-6.1
  • Inhibitors
  • Migration
  • Nephroblastostatin
  • Netrinstatin-5C
  • Netrinstatin-5D
  • Proliferation
  • Spondinstatin-1
  • Wispostatin-2
  • Wispostatin-3

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

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