Beijing An Zhen Hospital, Capital Medical University, 100029 Beijing, China;
Key Laboratory of Upper Airway Dysfunction-related Cardiovascular Diseases, Beijing Institute of Heart Lung and Blood Vessel Disease, 100029 Beijing, China.
Proc Natl Acad Sci U S A. 2018 Jul 17;115(29):E6927-E6936. doi: 10.1073/pnas.1721521115. Epub 2018 Jul 2.
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 mice ( SExos) were taken up by aortic endothelial cells, which severely impaired endothelial function in nondiabetic mice. The exosomal proteins, rather than RNAs, mostly account for SExos-induced endothelial dysfunction. Comparative proteomics analysis showed significant increase of arginase 1 in SExos. Silence or overexpression of arginase 1 confirmed its essential role in 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.
外泌体在血液中含量丰富，可将各种分子递送到靶细胞。内皮细胞直接暴露于循环物质中。然而，内皮细胞如何对血清外泌体（SExos）作出反应以及其在糖尿病相关血管病变中的意义尚未被探索。在本研究中，我们表明，糖尿病小鼠的 SExos（SExos）被主动脉内皮细胞摄取，这严重损害了非糖尿病小鼠的内皮功能。外泌体蛋白，而不是 RNA，主要导致 SExos 诱导的内皮功能障碍。比较蛋白质组学分析显示 SExos 中精氨酸酶 1 的显著增加。精氨酸酶 1 的沉默或过表达证实了其在 SExos 诱导的内皮功能障碍中的重要作用。这项研究证明 SExos 将精氨酸酶 1 蛋白递送到内皮细胞，代表了糖尿病内皮功能障碍发展过程中的一种细胞机制。该结果扩展了监测血管稳态的血液传播物质的范围。
