Association of deficiencies of catechol-O-methyltransferase and 2-methoxyestradiol with preeclampsia

Evaluation of: Kanasaki K, Palmsten K, Sugimoto H et al. Deficiency in catechol-O-methyltransferase and 2-methoxyoestradiol is associated with pre-eclampsia. Nature 453 (7198), 1117-1121 (2008). Despite recent advances in the understanding of dysregulation of placenta-derived anti-angiogenic factors in preeclampsia, the etiology and pathogenesis of this disorder remain elusive. Catechol-O-methyltransferase (COMT) generates 2-methoxyestradiol (2-ME) in the human placenta and has been shown to have decreased activity in the placenta in severe preeclampsia. Kanasaki and colleagues performed a series of experiments in a Comt ^-/- mouse model, showing that decreased COMT activity and subsequent decreased 2-ME levels resulted in the clinical, histologic and molecular changes characteristic of preeclampsia. Furthermore, both the preeclampsia-like clinical features and characteristic angiogenic abnormalities completely resolved in rescue experiments with 2-ME. In addition, circulating levels of 2-ME were lower in eight women with preeclampsia compared with 13 normotensive pregnant controls. These preliminary data suggest that 2-ME may serve both as a marker and as a therapeutic target in preeclampsia; thus, setting the stage for future comprehensive validation studies in larger patient cohorts.