Pre-eclampsia is a complex multisystem disorder

Thus, early placental development may be affected through dysregulated vascular development and function secondary to NAD(P)H oxidase-mediated altered gene expression [48, 213]

Pre-eclampsia is a complex multisystem disorder

Pre-eclampsia is a complex multisystem disorder

Preeclampsia is a complex multisystem disorder that can affect previously normotensive women. It is a leading cause of maternal and fetal morbidity and mortality worldwide, occurring in 3% to 14% of pregnancies [179, 180] . Preeclampsia clinically presents as a blood pressure reading > 140/90 mm Hg, taken on two separate occasions at least 6 hours apart along with proteinuria (≥ 0.3 g protein in a 24-hour urine specimen or persistent 1+ (30 mg/dL) protein on dipstick) after 20 weeks of gestation.

Members of the family of NAD(P)H oxidases are important generators of the SO anion in many cells, including trophoblasts and vascular endothelial cells. Increased SO anion production through activation of these enzymes may occur through one of several physiological mechanisms, and has been implicated in the pathogenesis of some vascular diseases [209]. Autoantibodies against the angiotensin receptor AT1, particularly the second loop (AT1-AA) [210], can stimulate NAD(P)H oxidase, leading to increased generation of ROS. In cultured trophoblast and smooth muscle cells, the AT1 receptor of preeclamptic women has been observed to promote both the generation of the SO anion and overexpression of NAD(P)H oxidase [211]. Between 6 and 8 weeks of gestation, active placental NAD(P)H yields significantly more SO anion than is produced during full-term [212].

Thus, early placental development may be affected through dysregulated vascular development and function secondary to NAD(P)H oxidase-mediated altered gene expression [48, 213]. Preeclamptic women produce ROS and exhibit higher NAD(P)H expression than those without the disease [211]. More specifically, it has been reported that women with early-onset preeclampsia produce higher amounts of the SO anion than women with late-onset disease [212]. Levels of TNF-α, and oxLDL are increased in preeclampsia and have been shown to activate the endothelial isoform of NAD(P)H oxidase been, ultimately resulting in increased levels of the SO anion [209]. The mechanism of placental NAD(P)H activation is still unclear, but the above findings may assist in elucidating the role of OS in the pathogenesis of placental dysfunction in reproductive diseases such as preeclampsia.

 

Ashok Agarwal, Anamar Aponte-Mellado, Beena J Premkumar, Amani Shaman & Sajal Gupta Reproductive Biology and Endocrinology volume 10, Article number: 49 (2012)