Antiangiogenic property of human thrombin

Barden Chan, Jaime R Merchan, Sujata Kale, Vikas P. Sukhatme

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Using protein chromatography, we purified and identified human prothrombin from human plasma as antiangiogenic. Prothrombin significantly inhibited endothelial cell tube formation in vitro at 10 μg/ml. Importantly, it also inhibited bFGF-induced angiogenesis in Matrigel-plug assays performed in mice. The proteolytic activity of thrombin appeared to be critical for the antiangiogenic activity of prothrombin. For example, thrombin exhibited inhibitory effects on endothelial cell tube formation in vitro at 10 U/ml. Addition of lepirudin, a specific inhibitor of thrombin, completely blocked prothrombin's and thrombin's antiangiogenic effects in vitro. We also assessed the importance of thrombin receptors in angiogenesis. Using small peptides that activate different protease-activated receptors (PARs), we showed that activation of PAR-1 led to inhibition of endothelial cell tube formation in vitro and bFGF-induced angiogenesis in vivo. Collectively, our data suggest that thrombin's proteolytic activity can be antiangiogenic.

Original languageEnglish
Pages (from-to)1-14
Number of pages14
JournalMicrovascular Research
Volume66
Issue number1
DOIs
StatePublished - Jul 1 2003
Externally publishedYes

Fingerprint

Thrombin
Prothrombin
Endothelial cells
Endothelial Cells
Proteinase-Activated Receptors
PAR-1 Receptor
Thrombin Receptors
Plasma (human)
Chromatography
Assays
Chemical activation
Peptides
In Vitro Techniques
Proteins

Keywords

  • Angiogenesis
  • Protease-activated receptors
  • Prothrombin
  • Thrombin

ASJC Scopus subject areas

  • Biochemistry
  • Cardiology and Cardiovascular Medicine

Cite this

Antiangiogenic property of human thrombin. / Chan, Barden; Merchan, Jaime R; Kale, Sujata; Sukhatme, Vikas P.

In: Microvascular Research, Vol. 66, No. 1, 01.07.2003, p. 1-14.

Research output: Contribution to journalArticle

Chan, Barden ; Merchan, Jaime R ; Kale, Sujata ; Sukhatme, Vikas P. / Antiangiogenic property of human thrombin. In: Microvascular Research. 2003 ; Vol. 66, No. 1. pp. 1-14.
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