Molecular pathogenesis of preeclampsia
- As part of our overall goal of understanding the complex mechanisms underlying hypertensive disorders, we have recently begun to focus on a new line of investigation - the molecular pathogenesis of preeclampsia.
- Defined by the clinical constellation of hypertension and renal disease in the last trimester of pregnancy, preeclampsia impacts up to 10% of pregnancies and is a leading cause of maternal and fetal morbidity and mortality. Despite its common occurrence and serious consequences, progress in understanding the pathophysiology of this disorder has been slow. Clinical studies have been limited by the difficulty of testing hypotheses in an urgent, high-risk setting. Basic research has been hampered by the lack of an animal model that fully recapitulates the clinical disorder.
- We recently identified and characterized a genetic murine model (BPH/5) that spontaneously develops the relevant clinical sequelae of the disorder including development of frank hypertension and renal disease in the last trimester of pregnancy that resolves upon delivery.
This model provides an exciting new opportunity for elucidating the molecular mechanisms of this devastating human disease, and a host of studies are ongoing including:
- analysis of several candidate molecules including VEGF and reactive oxygen species
- reciprocal embryo transfer experiments in the context of lentiviral-mediated gene manipulation of blastocysts
- mRNA, miRNA and protein profiling of BPH/5 placentas
- genetic mapping of the preeclampsia locus
Unsupervised hierarchical clustering analysis of differentially regulated miRNAs across BPH/5 mouse placenta Class I, II and III compared to control C57Bl/6 placenta.