Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 115, Issue 29, Pages E6927-E6936Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1721521115
Keywords
exosome; arginase 1; endothelium; nitric oxide; diabetes
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Funding
- Research Grants Council of Hong Kong [C4024-16W, T12-402/13M]
- National Natural Science Foundation of China [31741064, 91339117, 81471082, 81561128017]
- National Basic Research Program of China [2012CB517805]
- Beijing Natural Science Foundation [5122028]
- Hong Kong Scholarship Program
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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/dbSExos-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.
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