Differential miRNA expression analysis of extracellular vesicles from brain microvascular pericytes in spontaneous hypertensive rats

  • 55 Accesses



This study is to explore the exact roles of extracellular vesicle (EVs) miRNAs from brain microvascular pericytes in the pathogenesis of hypertension.


Forty-eight significantly differentially expressed miRNAs were identified, of which 17 were found to be upregulated and 31 were found to be downregulated in brain microvascular pericytes of spontaneous hypertensive rats, compared with that of normotension Wistar Kyoto rats. The GO enrichment analysis verified that the target genes were enriched in signaling pathways and molecular functions, such as metal ion binding, nucleotide binding and ATP binding. The KEGG analysis indicated that the target genes were enriched in Linoleic acid, alpha-linolenic acid and sphingolipid metabolism pathways.


Several EV derived miRNAs, such as miR-21-5p, let-7c-5p and let-7a-5p, were found to be abnormally expressed in brain microvascular pericytes obtained from spontaneous hypertensive rats, compared with that of normotension Wistar Kyoto rats. The results of our research provide more insights into the functional link between brain microvascular pericytes and the pathogenesis of hypertension.

This is a preview of subscription content, log in to check access.

Access options

Buy single article

Instant unlimited access to the full article PDF.

US$ 39.95

Price includes VAT for USA

Subscribe to journal

Immediate online access to all issues from 2019. Subscription will auto renew annually.

US$ 199

This is the net price. Taxes to be calculated in checkout.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7



Untranslated regions


Extracellular vesicles


Spinal cord injury


Transmission electron microscopy


Nanoparticle tracking analysis


Kyoto Encyclopedia of Genes and Genomes


Spontaneous hypertensive rats


Wistar Kyoto rats


Gene ontology


Biology process


Cellular component


Molecular function


Solute carrier family 7 member 1


  1. Alipoor SD et al (2019) Serum exosomal miRNAs are associated with active pulmonary tuberculosis. Dis Markers 2019:1907426.

  2. Armulik A, Genove G, Betsholtz C (2011) Pericytes: developmental, physiological, and pathological perspectives, problems, and promises. Dev Cell 21:193–215.

  3. Bhome R, Del Vecchio F, Lee GH, Bullock MD, Primrose JN, Sayan AE, Mirnezami AH (2018) Exosomal microRNAs (exomiRs): small molecules with a big role in cancer. Cancer Lett 420:228–235.

  4. Borodzicz S, Czarzasta K, Kuch M, Cudnoch-Jedrzejewska A (2015) Sphingolipids in cardiovascular diseases and metabolic disorders. Lipids Health Dis 14:55.

  5. Carrick D et al (2018) Hypertension, microvascular pathology, and prognosis after an acute myocardial infarction. Hypertension 72:720–730.

  6. Cengiz M et al (2015) Circulating miR-21 and eNOS in subclinical atherosclerosis in patients with hypertension. Clin Exp Hypertension 37:643–649.

  7. Chen X, Liang H, Zhang J, Zen K, Zhang CY (2012) Secreted microRNAs: a new form of intercellular communication. Trends Cell Biol 22:125–132.

  8. Ebrahimkhani S et al (2017) Exosomal microRNA signatures in multiple sclerosis reflect disease status. Sci Rep 7:14293.

  9. Enright AJ, John B, Gaul U, Tuschl T, Sander C, Marks DS (2003) MicroRNA targets in Drosophila. Genome Biol 5:R1.

  10. Fenger M, Linneberg A, Jeppesen J (2015) Network-based analysis of the sphingolipid metabolism in hypertension. Front Genet 6:84.

  11. Ferland-McCollough D, Slater S, Richard J, Reni C, Mangialardi G (2017) Pericytes, an overlooked player in vascular pathobiology. Pharmacol Ther 171:30–42.

  12. Gaceb A, Barbariga M, Ozen I, Paul G (2018) The pericyte secretome: potential impact on regeneration. Biochimie 155:16–25.

  13. Garcia-Contreras M, Shah SH, Tamayo A, Robbins PD, Golberg RB, Mendez AJ, Ricordi C (2017) Plasma-derived exosome characterization reveals a distinct microRNA signature in long duration type 1 diabetes. Sci Rep 7:5998.

  14. Hannafon BN et al (2016) Plasma exosome microRNAs are indicative of breast cancer. Breast Cancer Res 18:90.

  15. Hornick NI, Huan J, Doron B, Goloviznina NA, Lapidus J, Chang BH, Kurre P (2015) Serum exosome MicroRNA as a minimally-invasive early biomarker of AML. Sci Rep 5:11295.

  16. Langmead B, Trapnell C, Pop M, Salzberg SL (2009) Ultrafast and memory-efficient alignment of short DNA sequences to the human genome. Genome Biol 10:R25.

  17. Li H et al (2016) MicroRNA-21 Lowers blood pressure in spontaneous hypertensive rats by upregulating mitochondrial translation. Circulation 134:734–751.

  18. Liu X, Fortin K, Mourelatos Z (2008) MicroRNAs: biogenesis and molecular functions. Brain Pathol 18:113–121.

  19. Liu X, Yuan W, Yang L, Li J, Cai J (2019) miRNA profiling of exosomes from spontaneous hypertensive rats using next-generation sequencing. J Cardiovasc Trans Res 12:75–83.

  20. Majzunova M, Dovinova I, Barancik M, Chan JY (2013) Redox signaling in pathophysiology of hypertension. J Biomed Sci 20:69.

  21. Mao X, Cai T, Olyarchuk JG, Wei L (2005) Automated genome annotation and pathway identification using the KEGG Orthology (KO) as a controlled vocabulary. Bioinformatics 21:3787–3793.

  22. Murthy M, Kurz T, O'Shaughnessy KM (2017) WNK signalling pathways in blood pressure regulation. Cell Mol Life Sci 74:1261–1280.

  23. Ren W et al (2019) Exosomal miRNA-107 induces myeloid-derived suppressor cell expansion in gastric cancer. Cancer Manage Res 11:4023–4040.

  24. Sekar D, Shilpa BR, Das AJ (2017) Relevance of microRNA 21 in different types of hypertension. Curr Hypertens Rep 19:57.

  25. Serne EH, de Jongh RT, Eringa EC, Ijzerman RG, Stehouwer CD (2007) Microvascular dysfunction: a potential pathophysiological role in the metabolic syndrome. Hypertension 50:204–211.

  26. Shen E, Diao X, Wei C, Wu Z, Zhang L, Hu B (2010) MicroRNAs target gene and signaling pathway by bioinformatics analysis in the cardiac hypertrophy. Biochem Biophys Res Commun 397:380–385.

  27. Spijkers LJ et al (2011) Hypertension is associated with marked alterations in sphingolipid biology: a potential role for ceramide. PLoS ONE 6:e21817.

  28. Sugimachi K et al (2015) Identification of a bona fide microRNA biomarker in serum exosomes that predicts hepatocellular carcinoma recurrence after liver transplantation. Br J Cancer 112:532–538.

  29. Tang Y, Zhao Y, Song X, Song X, Niu L, Xie L (2019) Tumor-derived exosomal miRNA-320d as a biomarker for metastatic colorectal cancer. J Clin Lab Anal 33:e23004.

  30. Tsukamoto I, Sugawara S (2018) Low levels of linoleic acid and alpha-linolenic acid and high levels of arachidonic acid in plasma phospholipids are associated with hypertension. Biomed Reps 8:69–76.

  31. Villarroya-Beltri C, Gutierrez-Vazquez C, Sanchez-Madrid F, Mittelbrunn M (2013) Analysis of microRNA and protein transfer by exosomes during an immune synapse. Methods Mol Biol 1024:41–51.

  32. Wu Q, Yuan X, Han R, Zhang H, Xiu R (2019) Epitranscriptomic mechanisms of N6-methyladenosine methylation regulating mammalian hypertension development by determined spontaneously hypertensive rats pericytes. Epigenomics.

  33. Xin H et al (2012) Exosome-mediated transfer of miR-133b from multipotent mesenchymal stromal cells to neural cells contributes to neurite outgrowth. Stem Cells 30:1556–1564.

  34. Yuan X, Wu Q, Liu X, Zhang H, Xiu R (2018) Transcriptomic profile analysis of brain microvascular pericytes in spontaneously hypertensive rats by RNA-Seq. Am J Transl Res 10:2372–2386

  35. Yuan X et al (2019) Exosomes derived from pericytes improve microcirculation and protect blood-spinal cord barrier after spinal cord injury in mice. Front Neurosci 13:319.

  36. Zhang J, Li S, Li L, Li M, Guo C, Yao J, Mi S (2015) Exosome and exosomal microRNA: trafficking, sorting, and function. Genomics Proteomics Bioinf 13:17–24.

Download references


This study was supported by the innovation fund of the Chinese Academy of Medical Sciences and Peking Union Medical College (Grant Nos. 3332014006 and 3332015123), the CAMS Initiative for Innovative Medicine (CAMS-I2M) (Grant No. 2016-I2M-3-006) and National Natural Science Foundation of China (Grant No. 81801433).

Author information

Correspondence to Xiaochen Yuan or Honggang Zhang.

Ethics declarations

Conflict of interest

The authors have no conflicts of interest to declare.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary file1 (XLSX 49460 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Wu, Q., Yuan, X., Li, B. et al. Differential miRNA expression analysis of extracellular vesicles from brain microvascular pericytes in spontaneous hypertensive rats. Biotechnol Lett (2020) doi:10.1007/s10529-019-02788-x

Download citation


  • Extracellular vesicle microRNA
  • Microvascular pericytes
  • Hypertensive
  • Pathway analysis