Angiogenic factors and natural killer (NK) cells in the pathogenesis of preeclampsia

Abstract

Preeclampsia is a pregnancy-specific complex disease in which numerous genetic, immunological and environmental factors interact. Characterized by new onset hypertension, proteinuria and edema after 20 weeks of gestation, preeclampsia is often complicated by small-for-gestational-age (SGA) babies and preterm delivery, and is therefore a significant cause of maternal and fetal morbidity and mortality. The only definitive treatment of preeclampsia is delivery of the placenta. Recent data suggest that the anti-angiogenic state induced by excess circulating anti-angiogenic factors of placental origin may be responsible for the clinical signs and symptoms of preeclampsia. Natural killer (NK) cells at the maternal/fetal interface, which are thought to play an important role in normal placental development, have been noted recently to induce angiogenic factors and vascular remodeling. Moreover, genetic studies suggest that susceptibility to preeclampsia may be influenced by polymorphic HLA-C ligands and killer cell receptors (KIR) present on NK cells. This review summarizes our current understanding of the role of angiogenic factors and NK cells in the pathogenesis of preeclampsia.

Depletion of Invariant NKT Cells Reduces Inflammation-Induced Preterm Delivery in Mice

“…Although DCs contribute to an immunosuppressive atmosphere over the course of gestation, they possess the capacity to contribute to proinflammatory responses upon pathogenic activation. Driven by pathogens and inflammatory signals, DCs undergo a complex maturation process, which not only leads to enhanced expression of costimulatory molecules and increased formation of stable MHC/peptide complexes but also to cytokine secretion modulating T cell activation and expansion, synthesis of chemokines and chemokine receptors, and regulation of T cell and DC trafficking (31). In our study, depletion of iNKT cells decreased the expression of costimulatory molecules CD40, CD80, and CD86 in decidual DCs and the number of activated decidual DCs, suggesting that iNKT cells have an impact on inflammation-induced decidual DC maturation and activation.…”

Angiogenic Factors in Preeclampsia

“…Numerous pathways have been proposed to have key roles in inducing placental disease, including deficient heme oxygenase expression, placental hypoxia, genetic factors, corin deficiency, autoantibodies against the angiotensin receptor, oxidative stress, inflammation, altered natural killer cell signaling, deficient catechol-O-methyl transferase, complement activation, and more recently aberrant vasopressin production. 11,[55][56][57][58][59][60][61][62] Interestingly, several of these pathways were shown to increase placental production of the antiangiogenic factors in cell culture or animal models. However, human studies describing the temporal relationship between the angiogenic factors and the upstream pathways are still lacking before one can draw definitive conclusions.…”

Angiogenic Factors in Preeclampsia and Related Disorders

“…Thus other factors may concur to cause placental dysfunction. Various pathways including deficient heme oxygenase expression, genetic factors, oxidative stress, inflammation, altered natural killer cell signaling, and, more recently, deficient catechol-O-methyl transferase (Redman and Sargent 2005;Cudmore et al 2007;Kopcow and Karumanchi 2007;Kanasaki et al 2008;Zhao et al 2009) have been also proposed to have key roles in inducing placental disease (Fig. 3).…”