Abstract
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.
Financial & competing interests disclosure
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
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