Investigation of the miRNA transcriptome of umbilical cord vein and artery exosomes between IUGR and normal littermates showed significant differences between umbilical veins from normal (NV) and IUGR (IV) piglets. Similar patterns were observed in normal (NA) and IUGR (IA) umbilical arteries as well. Moreover, the miRNAs expession level was more stable in NV. Further analysis revealed that miRNAs related to angiogenesis exhibited aberrant expression in IUGR pigs. The miRNA expression patterns between IUGR and normal piglets showed great difference. Expression of miR-150 in the tissues and UCB exosomes of IUGR pigs was significantly decreased.
Ultimately, up-regulation of miR-150 was able to increase proliferation, migration and tube formation of Human umbilical vein endothelial cells (HUVECs), suggesting a pro-angiogenic role. Furthermore, the data demonstrated that UCB derived miRNAs participate in fetal epigenetic regulation during pregnancy, suggesting a novel possible explanation for abnormal embryologic vascular development and several congenital cardiovascular diseases.
(A) Differentially expressed (DE) miRNAs between NV (umbilical vein of normal) and IV (umbilical vein of IUGR), NA (umbilical artery of normal) and IA (umbilical artery of IUGR); Venn diagram of miRNAs expressed in NV, IV, NA and IA; (B) Analysis of miRNAs universally abundant across umbilical cord blood exosomes; (C) Cluster analysis of all expressed miRNAs. (D) GO and KEGG analysis of miRNAs differentially expressed (DE) between IUGR and normal littermates. Note: Red indicated the high expression of miRNA; Green indicated the low expression of miRNA.