Vascular wall microenvironment: exosomes secreted by adventitial fibroblasts induced vascular calcification

Autor: Ming-Hui Zheng, Su-Kang Shan, Xiao Lin, Feng Xu, Feng Wu, Bei Guo, Fu-Xing-zi Li, Zhi-Ang Zhou, Yi Wang, Li-Min Lei, Ke-Xin Tang, Jia-Yue Duan, Yun-Yun Wu, Ye-Chi Cao, Xiao-Bo Liao, Ling-Qing Yuan
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Journal of Nanobiotechnology, Vol 21, Iss 1, Pp 1-21 (2023)
Druh dokumentu: article
ISSN: 1477-3155
DOI: 10.1186/s12951-023-02000-3
Popis: Abstract Vascular calcification often occurs in patients with chronic renal failure (CRF), which significantly increases the incidence of cardiovascular events in CRF patients. Our previous studies identified the crosstalk between the endothelial cells (ECs) and vascular smooth muscle cells (VSMCs), and the paracrine effect of VSMCs, which regulate the calcification of VSMCs. Herein, we aim to investigate the effects of exosomes secreted by high phosphorus (HPi) -induced adventitial fibroblasts (AFs) on the calcification of VSMCs and the underlying mechanism, which will further elucidate the important role of AFs in high phosphorus vascular wall microenvironment. The conditioned medium of HPi-induced AFs promotes the calcification of VSMCs, which is partially abrogated by GW4869, a blocker of exosomes biogenesis or release. Exosomes secreted by high phosphorus-induced AFs (AFsHPi-Exos) show similar effects on VSMCs. miR-21-5p is enriched in AFsHPi-Exos, and miR-21-5p enhances osteoblast-like differentiation of VSMCs by downregulating cysteine-rich motor neuron 1 (Crim1) expression. AFsHPi-Exos and exosomes secreted by AFs with overexpression of miR-21-5p (AFsmiR21M-Exos) significantly accelerate vascular calcification in CRF mice. In general, AFsHPi-Exos promote the calcification of VSMCs and vascular calcification by delivering miR-21-5p to VSMCs and subsequently inhibiting the expression of Crim1. Combined with our previous studies, the present experiment supports the theory of vascular wall microenvironment. Graphical Abstract
Databáze: Directory of Open Access Journals
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