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Mueck AO et al.  
Angiogenetic and Anti-Angiogenetic Effects of Estradiol and its Metabolites

Journal of Clinical and Basic Cardiology 2001; 4 (2): 153-155

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Keywords: AngiogeneseÖstradiolÖstradiolmetabolitenangiogenesisestradiolestradiol metabolites

Atherosclerotic plaques in later stages exhibit marked presence of new micro vessels. Thus angiogenesis may be important for the development of atherosclerotic plaques and long-term anti-angiogenetic therapy may present an effective new anti-atherosclerotic approach. 2-Methoxyestradiol, an endogenous estradiol metabolite, has already been shown to be an effective anti-angiogenetic substance. In the present study 14 endogenous estradiol metabolites were tested on their angiogenetic and anti-angiogenetic properties and compared to the effect of their parent substance, 17ß-estradiol. Endothelial cells from human umbilical veins were used for the experiments. 17ß-estradiol showed a biphasic reaction on the proliferation of vascular endothelial cells. At low concentration it stimulated and at high concentrations it inhibited cell growth. The same pattern was observed for the hydroxylated A-ring metabolites. Methylation of these metabolites, however, completely abrogated the anti-proliferative effect at high concentrations, except for the metabolite 2-hydroxyestradiol. For the D-ring metabolites no marked changes were observed. These results indicate that in addition to 2-methoxyestradiol other endogenous estradiol metabolites are potent anti-angiogenetic substances at high dosages. Since some of these metabolites are almost devoid of any estrogenic property, they may be useful for long-term anti-angiogenetic therapy in both men and women. This should be of interest to clinical pharmacological research since it points to potential new aspects in the treatment of cardiovascular diseases.
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