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Novel function of ascorbic acid as an angiostatic factor
Hiromi Ashino1, Mariko Shimamura, Hiroshi Nakajima
1Department of Molecular Biology, The Tokyo Metropolitan Institute of Medical Science, Tokyo Metropolitan Organization for Medical Research, Tokyo, Japan. ashino@rinshoken.or.jp
Angiogenesis
|May 29, 2004
Summary
L-ascorbic acid (Asc) inhibits angiogenesis, the formation of new blood vessels, through antioxidant properties and collagen synthesis. This angiostatic effect suggests Asc may aid in treating angiogenic diseases and certain cancers.
Area of Science:
- Biochemistry
- Cell Biology
- Physiology
Background:
- Endothelial permeability is regulated by vascular endothelial cell growth factor and antioxidants.
- L-ascorbic acid (Asc) decreases endothelial permeability by enhancing endothelial barrier function.
- The anti-angiogenic (angiostatic) role of Asc remains largely uncharacterized.
Purpose of the Study:
- To investigate the role of L-ascorbic acid (Asc) in angiogenesis.
- To determine if Asc exhibits angiostatic properties in vitro and in vivo.
- To elucidate the mechanisms underlying Asc's potential anti-angiogenic effects.
Main Methods:
- In vitro assays using cultured bovine microvascular endothelial cells to assess tubular structure formation, plasminogen activator activity, proliferation, and migration.
- In vivo studies on chick chorioallantoic membrane (CAM) to evaluate angiogenesis during embryogenesis.
- Treatment with Asc, collagen synthesis inhibitor (l-azetidine 2-carboxylic acid), and antioxidant glutathione (GSH) to assess their effects on angiogenesis and hydrogen peroxide-induced tubular morphogenesis.
Main Results:
- Asc inhibited the formation of vessel-like tubular structures in endothelial cells and angiogenesis in CAM in a dose-dependent manner.
- Asc did not inhibit plasminogen activator activity, endothelial cell proliferation, or migration.
- Inhibition of collagen synthesis partially reversed Asc's angiostatic effect on CAM.
- Glutathione (GSH), an endogenous antioxidant, also inhibited angiogenesis and tubular morphogenesis, similar to Asc.
- Both Asc and GSH inhibited hydrogen peroxide-induced tubular morphogenesis.
Conclusions:
- L-ascorbic acid (Asc) possesses angiostatic properties, inhibiting angiogenesis through both its antioxidant activity and stimulation of collagen synthesis.
- The findings suggest Asc's angiostatic activity may contribute to host resistance against solid cancer growth and invasiveness.
- Asc may serve as a valuable supplementary therapy for various angiogenic diseases.