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Aspirin-triggered DHA metabolites inhibit angiogenesis
M Vara-Messler1,2, L Trevisi1, E Zulato3
1Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy.
Frontiers in Pharmacology
|March 12, 2025
Summary
Docosahexaenoic acid (DHA) and aspirin (ASA) inhibit new blood vessel formation in tumors. Their combined effect, particularly through DHA metabolites like 17R-hydroxy-DHA, shows significant anti-angiogenic properties in both lab and animal models.
Area of Science:
- Biochemistry
- Molecular Biology
- Cancer Research
Background:
- Blood vessels are crucial for tissue nourishment and immune surveillance.
- Abnormalities in blood vessel formation, or angiogenesis, are implicated in diseases like cancer.
- Docosahexaenoic acid (DHA) and aspirin (ASA) have shown potential anti-cancer effects, possibly by targeting angiogenesis.
Purpose of the Study:
- To investigate the anti-angiogenic effects of DHA and its metabolites.
- To determine the role of aspirin (ASA) in modulating DHA's anti-angiogenic activity.
- To explore the mechanisms behind DHA's effect on endothelial cells and new blood vessel formation.
Main Methods:
- In vitro assays (MTT, wound healing, Boyden, Matrigel) to assess endothelial cell proliferation, motility, and tube formation.
- In vivo Matrigel sponge model in mice to measure angiogenesis.
- Liquid chromatography-tandem mass spectrometry (LC-MS-MS) to identify lipid mediators.
Main Results:
- DHA significantly reduced endothelial cell migration and tube formation.
- Aspirin (ASA) enhanced DHA's anti-angiogenic effects, particularly through the metabolite 17(R)-hydroxy-DHA (17R-HDHA).
- 17R-HDHA and its metabolite 17R-ResolvinD1 reduced microvessel density in vivo.
Conclusions:
- DHA exhibits anti-angiogenic properties, which are potentiated by ASA through COX-2 acetylation.
- The metabolite 17R-HDHA is a key mediator of DHA's anti-angiogenic effects.
- These findings suggest a therapeutic potential for DHA and ASA in targeting tumor angiogenesis.
Keywords:
17(R)-hydroxy-docosahexaenoic acid (17(R)-HDHA)angiogenesisaspirin (ASA)docosahexaenoic acid (DHA)human umbilical vein endothelial cells (HUVEC)More Related Videos
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