miRNA Profiling of Exosomes from Spontaneous Hypertensive Rats by Next-Generation Sequencing

The role and miRNA expression profile of exosomes in hypertension remain largely unknown, therefore, next generation sequencing was used to define the miRNA expression profile of plasma exosomes in spontaneously hypertensive rats (SHRs), the most widely used animal model of human essential hypertension, and their controls, normotensive Wistar-Kyoto rats (WKYs). Results revealed that percentages of miRNA in the total small RNA isolated from WKYs and SHRs were not significantly different. Twenty-seven miRNAs were significantly differentially expressed (DE) between WKY and SHR exosomes, among which 23 were upregulated and 4 were downregulated in SHR exosomes compared with WKY exosomes. Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis of top 10 DE miRNAs identified hypertension-specific target genes/signaling pathways. In conclusion, our findings indicate the selective packing of miRNA cargoes into exosomes under hypertensive status, while facilitating the development of potential targets for the diagnosis, prevention and treatment of hypertension.外泌体（exosomes）及其microRNA（miRNA）表达谱在高血压中的作用，目前仍未得到充分阐明。因此，本研究采用下一代测序技术，对自发性高血压大鼠（SHRs，目前应用最广泛的人类原发性高血压动物模型）及其对照组——血压正常的Wistar-Kyoto大鼠（WKYs）的血浆外泌体miRNA表达谱进行了鉴定。研究结果显示，从WKYs与SHRs中分离得到的总小RNA中，miRNA所占比例无显著统计学差异。WKY与SHR外泌体间共有27种miRNA呈显著差异表达（DE），其中相较于WKY外泌体，SHR外泌体中有23种miRNA表达上调，4种表达下调。通过对排名前十的差异表达miRNA进行基因本体（GO）富集分析与京都基因与基因组百科全书（KEGG）通路分析，本研究筛选出了高血压特异性靶基因及信号通路。综上，本研究结果表明，高血压状态下外泌体对miRNA载荷存在选择性包裹现象，同时为开发用于高血压诊断、预防与治疗的潜在靶点提供了有力支撑。