Manipulating bioactivities of endothelial progenitor cell-derived exosomes for promoting angiogenesis in ischemic vascular diseases. (February 2023)

• Record Type: Journal Article
• Authors: Dong, Bing; Qiu, Yumin; Liu, Zhefu; Huang, Jinsheng; Wang, Zhichao; Tu, Qiang; Zhou, Zhe; He, Jiang; Wang, Yong; Liu, Xiaolin; Zhang, Jianning; Shuai, Xintao; Tao, Jun; Xia, Wenhao
• Is Part Of: Nano today. Volume 48(2023)
• Publication Date: 2023-02
• Subjects: CHD coronary heart disease -- EPCs endothelial progenitor cells -- ECs endothelial cells -- HUVECs human umbilical vein endothelial cells -- EPC-EXO exosomes secreted by endothelial progenitor cells -- C-EPC-EXO EPC-EXO from patients with coronary heart disease -- H-EPC-EXO EPC-EXO from healthy man -- miR-199a-3p microRNA-199a-3p -- QKI-5 RNA-binding protein Quaking isoform 5 -- 3′-UTR 3′-untranslated region -- α-SMA α-smooth muscle actin -- RT-PCR reverse transcription polymerase chain reaction -- cRGD cyclic cRGDfK peptide; Coronary heart disease -- Endothelial progenitor cells-derived exosomes -- Exosome manipulating; Nanotechnology -- Periodicals; Nanosciences -- Périodiques; 620.505
• DOI: 10.1016/j.nantod.2023.101758
• Languages: English
• ISSNs: 1748-0132

Abstract

Abstract: Exosomes paracrine-secreted by EPC (EPC-EXO) may exert strong pro-angiogenic effects, which offers a potential means to treat ischemic diseases. However, the mechanism of EPC-EXO-mediated angiogenesis remains unknown, and EPC-EXO shows poor homing to ischemic sites, which greatly limits the pro-angiogenic effect in vivo . We found that EPC-EXO from patients with coronary heart disease (C-EPC-EXO) was much less effective than EPC-EXO from healthy volunteers (H-EPC-EXO) in improving angiogenesis in murine hindlimb ischemia model. The miRNA sequencing and RT-PCR analyses detected abundant microRNA-199a-3p (miRNA-199a-3p) in C-EPC-EXO, and computational and luciferase reporter gene analyses further found that miR-199a-3p targeted the seed sequence of 4856–4862 in the 3′-untranslated region of RNA-binding protein Quaking isoform 5 (QKI-5) mRNA in 293T cells. Increasing the intracellular miR-199a-3p level of human umbilical vein endothelial cells (HUVECs) downregulated the QKI-5 gene expression and decreased angiogenesis, whereas inhibiting miR-199a-3p led to opposite results. Therefore, the miR-199a-3p-inhibited C-EPC-EXO promoted ECs-mediated angiogenesis more effectively than the original C-EPC-EXO. Besides, decorating C-EPC-EXO with cRGD enhanced targeting delivery to ischemic sites, further strengthening the pro-angiogenic effect of exosomes. Overall, manipulating the bioactivities of C-EPC-EXO through miR-199a-3p inhibition and cRGD decoration remarkably promotes ECs-mediated angiogenesis for treating ischemic vascular diseases. Graphical Abstract: The abundant miRNA-199a-3p in C-EPC-EXO targeted the QKI-5 mRNA to suppress angiogenesis both in vitro and in vivo. Manipulating the bioactivities of C-EPC-EXO through miR-199a-3p inhibition and cRGD decoration remarkably promotes ECs-mediated angiogenesis for treating ischemic vascular diseases. ga1 Highlights: The abundant miRNA-199a-3p in C-EPC-EXO targeted QKI-5 mRNA to suppress angiogenesis both in vitro and in vivo. The unfavorable content miR-199a-3p was indeed underlying cause for the weakened pro-angiogenic effects of C-EPC-EXO. Manipulating the bioactivities of C-EPC-EXO through miR-199a-3p inhibition and cRGD decoration remarkably promotes ECs-mediated angiogenesis for treating ischemic vascular diseases.