Integrated exosomal miRNA and transcriptome analysis of brain microvascular endothelial cells in spontaneously hypertensive rats.

Endothelial cells, which regulate arterial stiffness via endothelial-derived substances, are independently and strongly associated with hypertension. However, the exact roles of exosome miRNAs from brain endothelial cells in the development of hypertension are still not fully explored. Here, we investigated the miRNA functions systematically by examining both exosomal small RNA and mRNA of endothelial cells in Wistar Kyoto (WKY) rats versus spontaneously hypertensive rats (SHRs). Our findings revealed that miRNAs, representing ~60-70%, account for the majority of small RNAs. Moreover, we found 159 novel miRNAs in total from the unannotated reads across the diverse samples. Afterwards, 76 differentially expressed miRNAs (37 upregulated, 39 downregulated) and 1709 differentially expressed mRNAs (775 upregulated, 934 downregulated) were identified between SHRs and WKY rats, respectively. Finally, 647 genes targeted by 36 miRNAs came to our attention via identification of the target genes of those abnormal miRNAs. The differentially expressed target genes induced by miRNA changes were mapped to a number of genes involved in various gene functions and pathways. These changes lead to dysregulation of angiogenesis, axonogenesis, neuron-to-neuron synapses, focal adhesion, axon guidance, cell adhesion molecules (CAMs), adherens junction, and ECM-receptor interaction pathways. Together, our study revealed that the miRNAs are changed and contribute to the dysregulated functions and pathways of their target genes and provided more insights into their regulation mechanisms during mammalian hypertension development.