Exosomes from human umbilical cord mesenchymal stem cells protect aortas in Db/db mice characterized by combination of metabolomics and proteomics

• Published in: Archives of biochemistry and biophysics 2022-11, Vol.731, p.109430-109430, Article 109430
• Main Authors: Ling, Ming-ying, Yang, Xue-chun, Yu, Na, Song, Yi-ping, Zheng, Yu-jing, Tang, Cong-min, Ding, Wen-jing, Sun, Yan, Yan, Rong, Wang, Shao-peng, Li, Xue-hui, Gao, Hai-qing, Zhang, Zhen, Xing, Yan-qiu
• Format: Article
• Language: English
• Subjects: Animals; Aorta; Cardiovascular complication; Diabetes; Exosomes; Exosomes - metabolism; Humans; Mesenchymal stem cells; Mesenchymal Stem Cells - metabolism; Metabolomics; Mice; Proteomics; Umbilical Cord; Vascular Remodeling
• ISSN: 0003-9861; 1096-0384
• DOI: 10.1016/j.abb.2022.109430

Diabetic cardiovascular complication is a common systemic disease with high morbidity and mortality worldwide. We hypothesise that exosomes derived from human umbilical cord mesenchymal stem cells (hUCMSCs-exos) can rescue these disorders and alleviate vascular remodeling in diabetes. Morphological, non-targeted metabolomics and 4D label-free proteomics techniques were used to analyze the aortas of db/m mice as normal control group (NCA), saline treated db/db mice (DMA), and hUCMSCs-exos treated db/db mice (DMTA), and to clarify the molecular mechanism of the protection of hUCMSCs-exos in vascular remodeling from a new point of view. The results showed that 74 metabolites were changed significantly in diabetic aortas, of which 15 were almost restored by hUCMSCs-exos. In proteomics, 30 potential targets such as Stromal cell-derived factor 2-like protein 1, Leukemia inhibitory factor receptor, Peroxisomal membrane protein and E3 ubiquitin-protein ligase MYCBP2 were detected. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway-based analysis showed that Central carbon metabolism in cancer and Galactose metabolism pathway were up-regulated to near normal by hUCMSCs-exos in metabolomics, with janus associated kinase-signal transducer and activator of transcription (JAK-STAT) pathway displayed in proteomics. According to bioinformatics and integrated analysis, these targeted molecules of hUCMSCs-exos to attenuate the vascular remodeling were mainly associated with regulation of energy metabolism, oxidative stress, inflammation, and cellular communications. This study provided a reference for the therapy of diabetes-induced cardiovascular complications. [Display omitted] •Diabetic cardiovascular complication is a common systemic disease worldwide.•Metabolomics and proteomics are used to identify potential markers and mechanisms.•Exosomes from mesenchymal stem cells alleviate aortic remodeling in diabetic mice.•JAK-STAT signaling is enriched by proteomics in exosomes interference.