Molecular pathogenesis of preeclampsia: microRNA hypothesis

The discovery of micro RNA (miRNA) in 1993 by Ambros and colleagues has a huge influence in pathogenesis theory, diagnosis and treatment approach of some diseases. Some studies have conducted to seek the association alterations of miRNA expression to incidences and severity of preeclampsia (PE). We have reviewed some studies that conducted to seek the association of miRNA and PE and we discussed the role of various miRNAs in PE pathogenesis. In summary, we have shown that many researchers have given evident that the different placental and plasma miRNA expression is associated with PE. Some studies also identified the novel candidate of miRNAs (and their pathways) that may be of etiologic relevance in the pathogenesis of PE. Base on review, specific miRNA have a role to down regulate of anti apoptosis genes, regulate angiogenics growth factors such as angiogenin, vascular endothelial growth factor (VEGF) B (VEGF-β), cysteine-rich 61 (CYR61), Placental growth factor (PlGF) and VEGF-A that have a role in angiogenesis. miRNA also have a role in  survival, migration, and capillary tube formation of HUVEC by targeted of c-kit. Some miRNAs target genes that participate in immunologic dysfunction, cell adhesion, cell cycle, and signaling. miRNA also have a roles in endothelial cell response to hypoxia, cell differentiation, and survival. A miRNA influence calcium signaling through negative regulations of the calmodulin-coding mRNAs, Mef2a and Gata4, mainly in smooth muscle cells that contribute to PE pathogenesis. These investigations provide novel targets for further investigation of the pathogenesis of PE and these differential miRNAs may be potential markers for the diagnosis and provide a potential therapeutic target for PE. Further investigations on posttranscriptional regulation in PE to evaluate biologic effects of identified miRNAs (including confirmations of miRNA and target gene interactions) are needed