The biology of preeclampsia

Abstract

Preeclampsia is a systemic disease that results from placental defects and occurs in about 5-8% of pregnancies worldwide. Preeclampsia is a disease of many theories, wherein investigators put forward their favorite mechanistic ideas, each with a causal appeal for the pathogenesis of preeclampsia. In reality, the patho-mechanism of preeclampsia remains largely unknown. Preeclampsia, as diagnosed in patients today, is likely a heterogeneous collection of disease entities that share some common features but also show important differences. Therefore, one single mechanism may never be found to explain all the variants of preeclampsia. Current research must focus on evaluating such diverse mechanisms, as well as the possible common effector pathways. Here, we provide a discussion of several possible mechanisms and putative theories proposed for preeclampsia, with particular emphasis on the recent discovery of a new genetic mouse model offering new opportunities to explore experimental therapies.

Figure l. Patho-physiology of Hypertension in Preeclampsia

When compared to normal pregnancy, preeclampsia is associated with constricted, high resistance vessels, lower plasma volume, high sensitivity to vasoactive substances, presence of auto-antibodies against angiotenein type I (AT1) receptor, and low plasma level of 2-ME. PRA, plasma rennin activity; 2-ME, 2-methoxyestradiol.

Figure 2. The Role of COMT)/2-methoxyestradiol (2-ME in Pregnancy

In normal pregnancy, 2-ME may play a role in regulating hypoxia-inducible factor (HIF)-1α in diverse ways. In preeclampsia, low COMT/2-ME may induce accumulation of HIF-1α, vascular defect, placental hypoxia and inflammatory responses in the placenta. Such response may induce placental defects and result in suppression of placental-derived estradiol and further reduction in 2-ME levels. CYP450, cytochrome 450.

Figure 3. Biology of preeclampsia

Many different mechanisms have been reported for preeclampsia and they are listed here. NK cell, natural killer cell; 2-ME, 2-methoxyestradiol; HIFs, hypoxia-inducible factors; AT(1)-AAs, auto-antibodies for angiotensin receptor type I; VEGF, vascular endothelial growth factor; sEndoglin, soluble endoglin; sFlt1, soluble Fms-like tyrosine kinase-1.