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MiR\u2010126\u20103p is an important microRNA (miRNA) that regulates vascular structure and function, which can be transported through exosomes. However, the role of miR\u2010126\u20103p in vascular damage in SSc is still unclear. Therefore, we focused on the connection between miR\u2010126\u20103p and vascular damage in SSc, as well as investigated the potential role of miR\u2010126\u20103p in vascular damage in SSc. First, this study successfully extracted extracellular vesicles from clinical plasma samples and characterized the exosomes within them. Then, we predicted and screened the target pathway mammalian\/mechanistic target of rapamycin (mTOR) and the target gene SLC7A5 of miR\u2010126\u20103p through online databases. Next, we constructed SSc mice for in\u00a0vivo studies. The results showed that the expression of miR\u2010126\u20103p was decreased in the plasma exosomes, while the SLC7A5 expression, autophagy, and lipid peroxidation were increased in the aorta. Luciferase reporter gene assays demonstrated that miR\u2010126\u20103p can bind to SLC7A5, resulting in a decrease in its expression. In\u00a0vitro experiments have shown that exosomal miR\u2010126\u20103p can be internalized by human umbilical vein endothelial cells (HUVECs). The miR\u2010126\u20103p group exhibited enhanced cell viability and tube formation ability, along with increased expression of the vascular formation marker CD31. Additionally, miR\u2010126\u20103p downregulated the protein expression of SLC7A5 and LC3 in HUVECs, while upregulating the protein expression of mTOR, P62, PPAR\u03b3, and CPT\u20101. However, the effects of miR\u2010126\u20103p on HUVECs were counteracted by mTOR inhibitors and enhanced by mTOR activators. The results indicated that exosomal miR\u2010126\u20103p has the potential to protect against vascular injury in SSc by regulating the SLC7A5\/mTOR signalling pathway in HUVECs.<\/jats:p>","DOI":"10.1111\/sji.13354","type":"journal-article","created":{"date-parts":[[2024,1,16]],"date-time":"2024-01-16T12:43:45Z","timestamp":1705409025000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Exosomal <scp>miR<\/scp>\u2010126\u20103p: Potential protection against vascular damage by regulating the <scp>SLC7A5<\/scp>\/<scp>mTOR<\/scp> Signalling pathway in human umbilical vein endothelial cells"],"prefix":"10.1111","volume":"99","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-2162-7857","authenticated-orcid":false,"given":"Ke","family":"Zhu","sequence":"first","affiliation":[{"name":"Department of Dermatology, Dermatology Hospital Southern Medical University  Guangzhou Guangdong China"},{"name":"Department of 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