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Endothelial progenitor cells (EPCs), derived from bone marrow, play a key role in vascular health, but their function diminishes with aging and exposure to oxidised low\u2010density lipoprotein (ox\u2010LDL). This study investigates the potential of Xin\u2010Mai\u2010Long (XML), a traditional Chinese medicine used for chronic congestive heart failure, to delay EPC senescence and dysfunction induced by ox\u2010LDL. Our findings demonstrate that XML administration significantly attenuates ox\u2010LDL\u2010induced EPC senescence and dysfunction. RNA sequencing identified Gria2 as a crucial gene downregulated by ox\u2010LDL and restored by XML. Overexpression of Gria2 in EPCs similarly protected against ox\u2010LDL\u2010induced damage. Further analysis using Gene Ontology (GO) and KEGG enrichment revealed that the cAMP signalling pathway is significantly activated in response to XML and Gria2 overexpression. Notably, inhibition of cAMP with cis\u2010Epoxysuccinic Acid (CESA) diminished the protective effects of XML and Gria2, underscoring the importance of this pathway. In\u00a0vivo experiments using a rat carotid balloon injury model showed that both XML administration and transplantation of Gria2\u2010overexpressing EPCs reduced vascular damage. These results suggest that XML mitigates EPC senescence and dysfunction by upregulating Gria2 and activating the cAMP signalling pathway, offering a promising therapeutic strategy for managing ISR after PCI.<\/jats:p>","DOI":"10.1111\/jcmm.70682","type":"journal-article","created":{"date-parts":[[2025,7,10]],"date-time":"2025-07-10T17:15:06Z","timestamp":1752167706000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["<scp>XML<\/scp> Attenuates Ox\u2010<scp>LDL<\/scp>\u2010Induced Endothelial Progenitor Cell Senescence via Gria2 and <scp>cAMP<\/scp> Pathways"],"prefix":"10.1111","volume":"29","author":[{"given":"Jinjian","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Cardiology Guizhou Provincial People's Hospital  Guiyang China"},{"name":"Department of Cardiology, Integrated Traditional Chinese and Western Medicine Hospital Liangshan Yi Autonomous Prefecture  Xichang Sichuan 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