The two leading hypothesis regarding the molecular mechanisms and etiology of preeclampsia, and the Mexican experience in the world context

Autores: Sánchez Rodríguez Elly Natty, Nava Salazar Sonia, Morán Villota Carlos, Romero Arauz Juan Fernando, Cerbón Cervantes Marco Antonio

Resumen

Although preeclampsia (PE) is one of the most severe complications of pregnancy, its etiology is still unknown. The current contribution analyzes epidemiological data in Mexico, as well as the molecular mechanisms of PE, all within the context of the two principal hypotheses of PE, immune maladaptation and the placental ischemia.The immune maladaptation hypothesis focuses on the immune response during placental development, which depends greatly on the genotypes of the maternal KIR receptors of Natural Killer (NK) cells and their ligands in the fetus that can lead to the receptor-ligand recognition necessary for adequate angiogenesis during the critical stages of decidual spiral arteriole remodeling. Genetic studies suggest that KIR receptors are indeed associated with the prevalence of PE, and specifically that the inhibition of NK cells predisposes women to PE. The placental ischemia hypothesis focuses on the reduced angiogenic and increased anti-angiogenic factors observed in women with PE. In the trophoblast of these women there is an overexpression of HIFα, which can induce the overexpression of non-angiogenic factors and inhibitors of trophoblast differentiation, such as the transforming growth factor beta3 (TGF-β3) and Hash-2. These observations coincide with the phenotypes found in the placentas of PE patients, where an immature trophoblast leads to an inadequate invasion. The molecular mechanisms related to the overexpression of HIF-α in women with PE could be related to the inhibition of its degradation. Under hypoxic conditions, HIF-α is not hydroxylated, preventing an interaction between HIF-α and pVHL, which is an important route for HIF-α degradation. We very recently found a difference in the expression of hydroxylases between women with severe PE on the one hand, and women with mild PE and normotensive pregnancies. Thus, indicating that it is an important mechanism that contributes to PE.

Palabras clave: Preeclampsia natural killer cells KIR receptors angiogenesis hypoxia-inducible factor.

2010-10-07   |   1,183 visitas   |   Evalua este artículo 0 valoraciones

Vol. 62 Núm.3. Mayo-Junio 2010 Pags. 252-260 Rev Invest Clin 2010; 62(3-ENGLISH)