Abstract | AIMS/HYPOTHESIS: METHODS: RESULTS:
Kallikrein- binding protein specifically inhibited proliferation and induced apoptosis in retinal capillary endothelial cells. Intravitreal injection of KBP inhibited retinal neovascularization in an OIR model. Moreover, KBP decreased vascular leakage in the retina, iris and choroid in rats with OIR. Blockade of kinin receptors by specific antagonists showed significantly weaker inhibition of endothelial cells, when compared to that of KBP, suggesting that the anti-angiogenic activity of KBP is not through inhibiting kallikrein activity or kinin production. KBP competed with (125)I-VEGF for binding to endothelial cells and down-regulated VEGF production in endothelial cells and in the retina of the OIR rat model. CONCLUSION/INTERPRETATION:
Kallikrein- binding protein is a multi-functional serpin, and its vascular activities are independent of its interactions with the kallikrein-kinin system. Inhibition of VEGF binding to its receptors and down-regulation of VEGF expression could represent a mechanism for the vascular activities of KBP.
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Authors | G Gao, C Shao, S X Zhang, A Dudley, J Fant, J-X Ma |
Journal | Diabetologia
(Diabetologia)
Vol. 46
Issue 5
Pg. 689-98
(May 2003)
ISSN: 0012-186X [Print] Germany |
PMID | 12743698
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Carrier Proteins
- DNA Primers
- Recombinant Proteins
- Serpins
- Vascular Endothelial Growth Factor A
- kallistatin
- DNA
|
Topics |
- Animals
- Apoptosis
- Base Sequence
- Capillary Permeability
(physiology)
- Carrier Proteins
(genetics, physiology)
- Cell Line
- Cell Survival
- Cloning, Molecular
- DNA
(biosynthesis)
- DNA Primers
- Endothelium, Vascular
(pathology, physiopathology)
- Escherichia coli
- Ischemia
(complications)
- Neovascularization, Pathologic
(prevention & control)
- Polymerase Chain Reaction
- Rats
- Rats, Inbred BN
- Recombinant Proteins
(metabolism)
- Retina
(pathology)
- Retinal Vessels
(pathology)
- Reverse Transcriptase Polymerase Chain Reaction
- Serpins
(genetics, physiology)
- Vascular Endothelial Growth Factor A
(antagonists & inhibitors, physiology)
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