Research Paper|Volume 11, Issue 24|pp 12147—12164

Hematoma-derived exosomes of chronic subdural hematoma promote abnormal angiogenesis and inhibit hematoma absorption through miR-144-5p

Chuang Gao^1,², Zhitao Gong^1,², Dong Wang^1,², Jinhao Huang^1,², Yu Qian^1,², Meng Nie^1,², Weiwei Jiang^1,², Xuanhui Liu^1,², Hongliang Luo^1,², Jiangyuan Yuan^1,², Tangtang Xiang^1,², Shuo An^1,², Wei Quan^1,², Huijie Wei^1,², Jianning Zhang^1,², Rongcai Jiang^1,²

¹Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, China
²Tianjin Neurological Institute, Key Laboratory of Post-Neuroinjury Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin, China

* Co-first authors

Received: September 15, 2019Accepted: November 19, 2019Published: December 16, 2019

https://doi.org/10.18632/aging.102550

Copyright © 2019 Gao et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Exosomes are small (30–150 nm diameter) lipid bilayer-enclosed vesicles found in all bodily fluids. We investigated whether exosomes play a role in chronic subdural hematoma (CSDH). Exosomes were identified and characterized using transmission electron microscopy and NanoSight particle tracking. The functions of hematoma-derived exosomes were evaluated in a rat model of acute subdural hematoma (SDH). The hematoma-derived exosomes inhibited hematoma absorption and exacerbated neurological deficits in SDH rats. We examined the effects of the exosomes on angiogenesis and cell permeability in human umbilical vein endothelial cells (HUVECs). Co-culture of exosomes with HUVECs revealed that the hematoma-derived exosomes were taken-in by the HUVECs, resulting in enhanced tube formation and vascular permeability. Additionally, there was a concomitant increase in ANG-2 expression and decrease in ANG-1 expression. Exosomes were enriched with microRNAs including miR-144-5p, which they could deliver to HUVECs to promote angiogenesis and increase membrane permeability. Overexpression of miR-144-5p in HUVECs and in SDH rats promoted abnormal angiogenesis and reduced hematoma absorption, which mimicked the effects of the hematoma-derived exosomes both in vitro and in vivo. Thus, hematoma-derived exosomes promote abnormal angiogenesis with high permeability and inhibit hematoma absorption through miR-144-5p in CSDH.