Novel approaches for mechanistic understanding and predicting preeclampsia

Abstract

Despite intense investigation, preeclampsia (PE) remains largely enigmatic. Relatively late onset of diagnostic signs and heterogeneous nature of the disease further contribute to poor understanding of its etiology and clinical management. There exist no concrete animal models that can provide mechanistic underpinnings for evaluating targeted therapeutic intervention. Poor cross-sectional findings with potential biochemical markers reported so far have proved counterintuitive and suggest a need for novel approaches to predict the early onset of disease. Because of the co-onset of local placental anomalies and systemic manifestation of symptoms, it is highly likely that serum from PE patients can provide a "blueprint" of causative factors. Proteomic and/or functional analysis of maternal serum are expected to predict the onset of disease ahead of manifestation of clinical symptoms. A serum-based predictive assay should overcome complexities resulting from the heterogeneous etiology of PE. This review attempts to address some of these issues and discuss the signature biochemical serum factors and propose new and better ways to predict PE.

Figure 1. Predicting preeclampsia: in vitro and in vivo biological approaches

An in vitro assay involves a matrigel-based interaction of endothelial cells and first trimester trophoblasts to form an endovascular fingerprint in response to pregnancy serum. Use of proteomics can reveal differences at the protein level and use of human serum in a pregnant mouse model in vivo is expected to provide confirmation of the impending clinical symptoms of preeclampsia.