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: Angiogenese, Östradiol, Östradiolmetaboliten, angiogenesis, estradiol, estradiol 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.
Journal of Clinical and Basic Cardiology 2001; 4 (2): 153-155
PDF Summary
Keywords: Angiogenese, Östradiol, Östradiolmetaboliten, angiogenesis, estradiol, estradiol 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.