Estradiol may be cardioprotective; however, the mechanisms involved remain unclear. Recent findings that estradiol attenuates neointima formation in estrogen receptor knockout mice suggest that the cardioprotective effects of estradiol may be mediated through estrogen receptor-independent mechanisms. Because 2-methoxyestradiol, an endogenous metabolite of estradiol with no affinity for estrogen receptors, is more potent than estradiol in inhibiting vascular smooth muscle cell growth, it is feasible that 2-methoxyestradiol mediates in part the cardioprotective effects of estradiol. To address this hypothesis, we examined the kinetics of 2-methoxyestradiol synthesis in vascular smooth muscle cells and endothelial cells. In human aortic smooth muscle cells, the Vmax, Km, and Vmax/Km ratio values for conversion of 2-hydroxyestradiol to 2-methoxyestradiol were 19±0.69 pmol · min-1 per 106 cells, 0.52±0.085 μmol/L, and 44±4.9 pmol · min-1 · μmol/L per 106 cells, respectively. In human coronary artery vascular smooth muscle cells, the Vmax, Km, and Vmax/Km ratio values for conversion of 2-hydroxyestradiol to 2-methoxyestradiol were 16±0.59 pmol · min-1 per 106 cells, 0.23±0.011 μmol/L, and 69±3.6 pmol · min-1 · μmol/L per 106 cells, respectively (all values significantly different compared with human aortic smooth muscle cells). Also, in human aortic versus coronary artery endothelial cells, the Vmax (33±0.24 versus 22±0.33 pmol · min-1 per 106 cells, respectively), Km (0.20±0.010 versus 0.099±0.014 μmol/L, respectively), and Vmax/Km (163±7.7 versus 243±41 pmol·min-1 · μmol/L per 106 cells, respectively) values were significantly different. Our results indicate that vascular smooth muscle and endothelial cells effectively metabolize 2-hydroxyestradiol to 2-methoxyestradiol. The lower Km and higher Vmax/Km ratio of human coronary versus aortic cells indicate a faster rate of local metabolism of 2-hydroxyestradiol to 2-methoxyestradiol in the coronary circulation at low levels of 2-hydroxyestradiol.
|Number of pages||5|
|Issue number||2 II|
|Publication status||Published - 2001|
- Coronary artery disease