Inflammation-induced endothelial cell-derived extracellular vesicles modulate the cellular status of pericytes

• Published in: Scientific reports Vol. 5; no. 1; p. 8505
• Main Authors: Yamamoto, Seiji, Niida, Shumpei, Azuma, Erika, Yanagibashi, Tsutomu, Muramatsu, Masashi, Huang, Ting Ting, Sagara, Hiroshi, Higaki, Sayuri, Ikutani, Masashi, Nagai, Yoshinori, Takatsu, Kiyoshi, Miyazaki, Kenji, Hamashima, Takeru, Mori, Hisashi, Matsuda, Naoyuki, Ishii, Yoko, Sasahara, Masakiyo
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 17.02.2015; Nature Publishing Group
• Subjects: 13/51; 14/19; 147/135; 38/61; 38/77; 42/34; 631/337/384/331; 631/80/86/820; 692/308/1426; 692/420/256/2516; 96/21; 96/31; Animals; Cell Communication; Cell culture; Cell interactions; Cerebrovascular system; Communication; Culture media; Cytokines; Endothelial cells; Endothelial Cells - metabolism; Extracellular vesicles; Extracellular Vesicles - metabolism; Flow cytometry; Gene expression; Gene Expression Profiling; Humanities and Social Sciences; Inflammation; Inflammation - genetics; Inflammation - metabolism; Inflammatory diseases; Mice; MicroRNAs - genetics; miRNA; mRNA; multidisciplinary; Pericytes; Pericytes - metabolism; RNA, Messenger - genetics; RNA, Messenger - metabolism; Science; Vascular endothelial growth factor
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep08505

Emerging lines of evidence have shown that extracellular vesicles (EVs) mediate cell-to-cell communication by exporting encapsulated materials, such as microRNAs (miRNAs), to target cells. Endothelial cell-derived EVs (E-EVs) are upregulated in circulating blood in different pathological conditions; however, the characteristics and the role of these E-EVs are not yet well understood. In vitro studies were conducted to determine the role of inflammation-induced E-EVs in the cell-to-cell communication between vascular endothelial cells and pericytes/vSMCs. Stimulation with inflammatory cytokines and endotoxin immediately induced release of shedding type E-EVs from the vascular endothelial cells and flow cytometry showed that the induction was dose dependent. MiRNA array analyses revealed that group of miRNAs were specifically increased in the inflammation-induced E-EVs. E-EVs added to the culture media of cerebrovascular pericytes were incorporated into the cells. The E-EV-supplemented cells showed highly induced mRNA and protein expression of VEGF-B, which was assumed to be a downstream target of the miRNA that was increased within the E-EVs after inflammatory stimulation. The results suggest that E-EVs mediate inflammation-induced endothelial cell-pericyte/vSMC communication and the miRNAs encapsulated within the E-EVs may play a role in regulating target cell function. E-EVs may be new therapeutic targets for the treatment of inflammatory diseases.