Assessment of therapeutic efficacy of miR-126 with contrast-enhanced ultrasound in preeclampsia rats

Preeclampsia is a pregnancy-specific syndrome characterized by high blood pressure and proteinuria, which has a pathophysiology of insufficient placental blood perfusion. MicroRNA-126 (miR-126), an angiogenesis-related miRNA, has been proved to play a significant role in endothelial cells response to ischemia in vitro and in vivo. However, whether miR-126 has therapeutic potential in vasculogenesis of preeclampsia placenta remains uncertain. In this study, we focused our attention on this unsolved problem. First, we established the preeclampsia animal model and over-expressed miR-126 in vivo using a specific agomir. Then we described the effects of miR-126 on placental vasculogenesis in preeclampsia rats, including the evaluation of placental blood perfusion using microbubbles-assisted contrast-enhanced ultrasonography (CEUS), placental histology, immunohistochemistry and pregnancy outcome. Finally, we investigated the possible target gene and pathway that miR-126 modulates. Together, our results showed that preeclampsia animal with over-expressed miR-126 had higher pup weight, placenta weight and proportion of live pups. Quantification of uteroplacental perfusion by CEUS and CD34 staining of placental tissue revealed that blood volume and microvessel density increased in miR-126 treated group. MiR-126 was related to PIK3R2 down-regulation and Akt activation within placenta, which had impacts on vascularization of placenta. Therefore, miR-126 may be an efficient gene therapy to promote angiogenesis and blood perfusion in preeclampsia placenta.