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Nitric oxide regulates Angiopoietin1/Tie2 expression after stroke
Alex Zacharek1, Jieli Chen, Chunling Zhang
1Department of Neurology, Henry Ford Health Sciences Center, Detroit, MI 48202, USA.
Neuroscience Letters
|June 10, 2006
Summary
The nitric oxide donor DETA-NONOate boosts Angiopoietin (Ang1)/Tie2 signaling in stroke rats, promoting blood vessel formation and stability. This suggests a potential therapeutic role for DETA-NONOate in stroke recovery.
Area of Science:
- Neuroscience
- Vascular Biology
- Pharmacology
Background:
- Stroke significantly impacts vascular integrity and angiogenesis.
- The Angiopoietin (Ang1)/Tie2 signaling pathway is crucial for regulating angiogenesis and vascular stability.
- Nitric oxide donors are being investigated for their therapeutic potential in neurological conditions.
Purpose of the Study:
- To investigate the effect of the nitric oxide donor DETA-NONOate on Angiopoietin (Ang1)/Tie2 expression and its role in angiogenesis and vascular integrity after stroke in rats.
- To determine if DETA-NONOate can promote angiogenesis in brain endothelial cells.
- To elucidate the mechanism by which DETA-NONOate influences vascular repair post-stroke.
Main Methods:
- Wistar rats underwent middle cerebral artery occlusion to induce stroke.
- Animals were treated with or without DETA-NONOate.
- Expression levels of Ang1, Tie2, and Occludin were measured in the ischemic border zone.
- In vitro studies assessed capillary tube formation in cultured brain endothelial cells treated with DETA-NONOate.
- The effect of neutralizing Ang1 antibody on DETA-NONOate-induced angiogenesis was evaluated.
Main Results:
- DETA-NONOate treatment significantly increased Ang1, Tie2, and Occludin expression in the ischemic border of stroke rats compared to controls.
- In vitro, DETA-NONOate promoted capillary tube formation in brain endothelial cells.
- Neutralizing Ang1 antibody diminished the pro-angiogenic effect of DETA-NONOate in vitro.
- These findings indicate a role for the Ang1/Tie2 axis in DETA-NONOate-mediated angiogenesis.
Conclusions:
- The nitric oxide donor DETA-NONOate enhances the Angiopoietin (Ang1)/Tie2 signaling pathway after stroke in rats.
- DETA-NONOate promotes angiogenesis and stabilizes newly formed vessels, potentially through the Ang1/Tie2 axis.
- These findings suggest that DETA-NONOate may be a promising therapeutic agent for promoting vascular repair and recovery after stroke.
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