Identifying immune mechanisms mediating the hypertension during preeclampsia

Abstract

Preeclampsia (PE) is a pregnancy-associated disorder that affects 5-8% of pregnancies and is a major cause of maternal, fetal, and neonatal morbidity and mortality. Hallmark characteristics of PE are new onset hypertension after 20 wk gestation with or without proteinuria, chronic immune activation, fetal growth restriction, and maternal endothelial dysfunction. However, the pathophysiological mechanisms that lead to the development of PE are poorly understood. Recent data from studies of both clinical and animal models demonstrate an imbalance in the subpopulations of CD4+ T cells and a role for these cells as mediators of inflammation and hypertension during pregnancy. Specifically, it has been proposed that the imbalance between two CD4+ T cell subtypes, regulatory T cells (Tregs) and T-helper 17 cells (Th17s), is involved in the pathophysiology of PE. Studies from our laboratory highlighting how this imbalance contributes to vasoactive factors, endothelial dysfunction, and hypertension during pregnancy will be discussed in this review. Therefore, the purpose of this review is to highlight hypertensive mechanisms stimulated by inflammatory factors in response to placental ischemia, thereby elucidating a role.

Keywords: cytokines; hypertension; inflammation; pregnancy.

Fig. 1.

Schematic illustrates our hypothesis that T cell profile altered in response to placental ischemia can lead to hypertension by stimulating B cell secretion of angiotensin II (ANG II) type I receptor (AT1-AA), thus leading to endothelin 1, reactive oxygen species, and enhanced vascular sensitivity to ANG II during pregnancy.