Exosomal Transfer of miR-185 Is Controlled by hnRNPA2B1 and Impairs Re-endothelialization After Vascular Injury

Yi Si; Fei Liu; Dongqing Wang; Chao Fang; Xiao Tang; Baolei Guo; Zhenyu Shi; Zhihui Dong; Daqiao Guo; Jianing Yue; Weiguo Fu

doi:10.3389/fcell.2021.619444

Exosomal Transfer of miR-185 Is Controlled by hnRNPA2B1 and Impairs Re-endothelialization After Vascular Injury

Front Cell Dev Biol. 2021 Apr 20:9:619444. doi: 10.3389/fcell.2021.619444. eCollection 2021.

Authors

Yi Si¹, Fei Liu¹, Dongqing Wang², Chao Fang¹, Xiao Tang¹, Baolei Guo¹, Zhenyu Shi¹, Zhihui Dong¹, Daqiao Guo¹, Jianing Yue¹, Weiguo Fu¹

Affiliations

¹ Department of Vascular Surgery, Zhongshan Hospital Fudan University, Shanghai, China.
² Department of Vascular and Endovascular Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Abstract

Dysfunction of endothelial cells (ECs) contributes to restenosis after vascular reconstruction for patients with coronary artery disease (CAD). The intercellular communication between ECs and vascular smooth muscle cells (VSMCs) might be critical in the development of restenosis and can be mediated by exosomes carrying functional microRNAs. miR-185 is reported to be associated with atherosclerosis, whether it plays a similar role in restenosis is unknown. In this study, we observed an elevated level of extracellular miR-185 in platelet-derived growth factor (PDGF)-stimulated VSMCs. The medium from PDGF-stimulated VSMCs promoted miR-185 expression in rat aortic ECs and inhibited EC angiogenesis. PDGF-stimulated VSMCs transferred miR-185 into ECs via exosomes. Furthermore, we found that the CXCL12 gene, a target of miR-185, is essential for the angiogenic potential of ECs. Exosomes derived from miR-185 mimic transfected VSMCs attenuated re-endothelialization after vascular injury. Moreover, we show that exosome-mediated miR-185 transfer is modulated by hnRNPA2B1. We also observed that hnRNPA2B1 is up-regulated during neointima formation and hnRNPA2B1 inhibition accelerates re-endothelialization and attenuates neointima formation following carotid injury. Taken together, our results indicate that exosomal miR-185 transfer from VSMCs to ECs is controlled by hnRNPA2B1 and impairs re-endothelialization after vascular injury.

Keywords: exosomes; hnRNPA2B1; miRNA transfer; re-endothelialization; vascular injury.