Novedades en pre-eclampsia

La pre-eclampsia (PE) es una condición que afecta al 5% de las embarazadas, puede matar a la embarazada y el feto, y puede dejar secuelas graves. Es una enfermedad misteriosa que se presta a todo tipo de teorías y tratamientos, ninguno de los cuales es satisfactorio.

Un nuevo estudio llevado a cabo en ratones, en el Beth Isreal Deaconess Medical Center, de Boston, parece que permite diagnosticar la enfermedad precozmente. Al parecer los animales que no producen un gen responsable de la producción de 2-metoxiestradiol (ME) desarrollan los signos de PE, incluyendo parto prematuro, hirpertensión, y alteración del desarrollo vascular. Cuando se administra el ME que le falta a los animales, se previene la PE. Los investigadores también estudiaron 13 mujeres con PE y tenían ligeramente disminuidos de ME. Un dato muy interesante, al margen de la PE, es que el ME está implicado en el origen de la esquizofrenia.

Deficiency in catechol-O-methyltransferase and 2-methoxyoestradiol is associated with pre-eclampsia.

Division of Matrix Biology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA.

Despite intense investigation, mechanisms that facilitate the emergence of the pre-eclampsia phenotype in women are still unknown. Placental hypoxia, hypertension, proteinuria and oedema are the principal clinical features of this disease. It is speculated that hypoxia-driven disruption of the angiogenic balance involving vascular endothelial growth factor (VEGF)/placenta-derived growth factor (PLGF) and soluble Fms-like tyrosine kinase-1 (sFLT-1, the soluble form of VEGF receptor 1) might contribute to some of the maternal symptoms of pre-eclampsia. However, pre-eclampsia does not develop in all women with high sFLT-1 or low PLGF levels, and it also occurs in some women with low sFLT-1 and high PLGF levels. Moreover, recent experiments strongly suggest that several soluble factors affecting the vasculature are probably elevated because of placental hypoxia in the pre-eclamptic women, indicating that upstream molecular defect(s) may contribute to pre-eclampsia. Here we show that pregnant mice deficient in catechol-O-methyltransferase (COMT) show a pre-eclampsia-like phenotype resulting from an absence of 2-methoxyoestradiol (2-ME), a natural metabolite of oestradiol that is elevated during the third trimester of normal human pregnancy. 2-ME ameliorates all pre-eclampsia-like features without toxicity in the Comt(-/-) pregnant mice and suppresses placental hypoxia, hypoxia-inducible factor-1alpha expression and sFLT-1 elevation. The levels of COMT and 2-ME are significantly lower in women with severe pre-eclampsia. Our studies identify a genetic mouse model for pre-eclampsia and suggest that 2-ME may have utility as a plasma and urine diagnostic marker for this disease, and may also serve as a therapeutic supplement to prevent or treat this disorder.

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