Protective role of small extracellular vesicles derived from HUVECs treated with AGEs in diabetic vascular calcification

Author:

Guo Bei,Shan Su-Kang,Xu Feng,Lin Xiao,Li Fu-Xing-zi,Wang Yi,Xu Qiu-Shuang,Zheng Ming-Hui,Lei Li-Min,Li Chang-Chun,Zhou Zhi-Ang,Ullah Muhammad Hasnain Ehsan,Wu Feng,Liao Xiao-Bo,Yuan Ling-QingORCID

Abstract

AbstractThe pathogenesis of vascular calcification in diabetic patients remains elusive. As an effective information transmitter, small extracellular vesicles (sEVs) carry abundant microRNAs (miRNAs) that regulate the physiological and pathological states of recipient cells. In the present study, significant up-regulation of miR-126-5p was observed in sEVs isolated from human umbilical vein endothelial cells (HUVECs) stimulated with advanced glycation end-products (A-EC/sEVs). Intriguingly, these sEVs suppressed the osteogenic differentiation of vascular smooth muscle cells (VSMCs) by targeting BMPR1B, which encodes the receptor for BMP, thereby blocking the smad1/5/9 signalling pathway. In addition, knocking down miR-126-5p in HUVECs significantly diminished the anti-calcification effect of A-EC/sEVs in a mouse model of type 2 diabetes. Overall, miR-126-5p is highly enriched in sEVs derived from AGEs stimulated HUVECs and can target BMPR1B to negatively regulate the trans-differentiation of VSMCs both in vitro and in vivo. Graphical Abstract

Funder

National Natural Science Foundation of China

Fundamental Research Funds for Central Universities of the Central South University

Key R&D Plan of Hunan Province

Natural Science Foundation of Hunan Province

Publisher

Springer Science and Business Media LLC

Subject

Pharmaceutical Science,Applied Microbiology and Biotechnology,Biomedical Engineering,Molecular Medicine,Medicine (miscellaneous),Bioengineering

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