Serum exosomes regulate vascular homeostasis in diabetes
Refereed conference paper presented and published in conference proceedings


摘要Exosomes are abundant in blood and the concentration was higher under diabetic condition. Vascular endothelial cells are constantly exposed to circulating exosomes which enclose various molecules that can be delivered to recipient cells through endocytosis and membrane ligand-receptor binding. Therefore, we aim to investigate how endothelial cells respond to serum exosomes and its implication in diabetes-associated vascular dysfunction.

Ex vivo study showed vascular endothelial cells are able to take up PKH67-labeled serum exosomes isolated from diabetic (db/db) mouse indicated by increased incorporation of fluorescence into endothelial cells. db/db serum exosomes severely impaired endothelium-dependent relaxation in non-diabetic db/m+ mice conduit and resistant arteries. The impaired vascular function can be rescued by co-treatment with heparin (exosome uptake inhibitor) or eNOS substrate L-arginine. In vitro study showed serum exosomes isolated from db/db mouse and diabetic Zucker (fa/fa) rat dose-dependently induced proliferation in primary cultured mouse (RAECs) and human umbilical vein endothelial cells (HUVECs) after 24-hr incubation. Proliferation of endothelial cells is linked to tight junction rearrangement. Screening of the expression of tight junction genes revealed significant decrease of Claudin 1 (Cldn1) and increase of tight junction protein 2 (ZO2).

Taken together, the present results suggest that serum exosomes inhibit NO production and impair endothelial function in mouse aorta. Serum exosomes also impair vascular integrity by altering the tight junction composition, which might contribute to diabetes-associated microvascular complications. (supported by RGF-CRF and RGC-GRF).
著者Yifan WANG, Huina ZHANG, Jian LIU, Dan QU, Yuhong HUANG, Xiaoyu TIAN, Li WANG, Yu HUANG
會議名稱Nature Conference on Cellular Metabolism
會議地點Xiamen, China

上次更新時間 2019-03-05 於 16:39