Serum exosomes mediate delivery of arginase 1 as a novel mechanism for endothelial dysfunction in diabetes

Huina Zhang*, Jian Liu, Dan Qu, Li Wang, Chi Ming Wong, Chi Wai Lau, Yuhong Huang, Yi Fan Wang, Huihui Huang, Yin Xia, Li Xiang, Zongwei CAI, Pingsheng Liu, Yongxiang Wei, Xiaoqiang Yao, Ronald Ching Wan Ma, Yu Huang

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

43 Citations (Scopus)

Abstract

Exosomes, abundant in blood, deliver various molecules to recipient cells. Endothelial cells are directly exposed to circulating substances. However, how endothelial cells respond to serum exosomes (SExos) and the implications in diabetes-associated vasculopathy have never been explored. In the present study, we showed that SExos from diabetic db/db mice (db/db SExos) were taken up by aortic endothelial cells, which severely impaired endothelial function in nondiabetic db/m+ mice. The exosomal proteins, rather than RNAs, mostly account for db/db SExos-induced endothelial dysfunction. Comparative proteomics analysis showed significant increase of arginase 1 in db/db SExos. Silence or overexpression of arginase 1 confirmed its essential role in db/db SExos-induced endothelial dysfunction. This study is a demonstration that SExos deliver arginase 1 protein to endothelial cells, representing a cellular mechanism during development of diabetic endothelial dysfunction. The results expand the scope of blood-borne substances that monitor vascular homeostasis.

Original languageEnglish
Pages (from-to)E6927-E6936
JournalProceedings of the National Academy of Sciences of the United States of America
Volume115
Issue number29
DOIs
Publication statusPublished - 17 Jul 2018

Scopus Subject Areas

  • General

User-Defined Keywords

  • Arginase 1
  • Diabetes
  • Endothelium
  • Exosome
  • Nitric oxide

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