Macrophage-derived exosomes induce inflammatory factors in endothelial cells under hypertensive conditions

Mayuko Osada-Oka, Masayuki Shiota, Yasukatsu Izumi, Masaki Nishiyama, Masako Tanaka, Takehiro Yamaguchi, Emi Sakurai, Katsuyuki Miura, Hiroshi Iwao

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

Hypertension is one of the most important cardiovascular risk factors and results in macrophage infiltration of blood vessels. However, how macrophages coordinate inflammatory responses with endothelial cells (ECs) remains unclear. In this study, we investigated whether exosomes upregulate the expression of inflammatory factors in ECs under hypertensive conditions. Hypertension was induced in rats by continuous infusion of angiotensin II (Ang II). Exosomes were purified from rat serum by density gradient and ultracentrifugation and used to stimulate human coronary artery ECs (HCAECs). Moreover, the interactions between HCAECs and exosomes from human THP-1-derived macrophages were analyzed. Administration of Ang II enhanced the expression of CD68, a macrophage marker, in rat hearts, suggesting enhanced infiltration of macrophages. In addition, the expression of intracellular adhesion molecule-1 (ICAM1) and plasminogen activator inhibitor-1 (PAI-1), a proinflammatory factor, was increased in hypertensive rat hearts compared with control rats. CD68 protein expression and an increase in the expression of some exosome markers were detected in exosomes from hypertensive rat serum. Moreover, the exosomes upregulated the expression levels of ICAM1 and PAI-1 in HCAECs. The level of miR-17, a negative regulator of ICAM1 expression, was markedly decreased in exosomes from hypertensive rat serum compared with exosomes from control rats. Interestingly, Ang II-stimulated THP-1-derived exosomes also enhanced the expression of ICAM1 and PAI-1 and contained reduced levels of miR-17 compared with exosomes from unstimulated cells. These results suggest that inflammation of ECs under hypertensive conditions is caused, at least in part, by macrophage-derived exosomes.

Original languageEnglish
Pages (from-to)353-360
Number of pages8
JournalHypertension Research
Volume40
Issue number4
DOIs
Publication statusPublished - 2017 Apr 1

Keywords

  • Angiotensin II
  • endothelial cells
  • endothelial cells
  • exosomes
  • exosomes
  • inflammation
  • inflammation
  • macrophages
  • macrophagesangiotensin II

ASJC Scopus subject areas

  • Internal Medicine
  • Physiology
  • Cardiology and Cardiovascular Medicine

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  • Cite this

    Osada-Oka, M., Shiota, M., Izumi, Y., Nishiyama, M., Tanaka, M., Yamaguchi, T., Sakurai, E., Miura, K., & Iwao, H. (2017). Macrophage-derived exosomes induce inflammatory factors in endothelial cells under hypertensive conditions. Hypertension Research, 40(4), 353-360. https://doi.org/10.1038/hr.2016.163