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Recent evidence revealed a new role for the vascular smooth muscle cell\u2013enriched (VSMC-enriched) long noncoding RNA (lncRNA) CARMN in endothelial angiogenesis and postischemic vascular repair. CARMN was downregulated in both human CLTI muscle tissue and murine ischemia models. In VSMCs, CARMN deficiency suppressed a specific miRNA-mediated paracrine signaling axis that regulates Hedgehog signaling. In mice, deleting CARMN caused impariment in capillary growth and blood flow recovery after limb ischemia, an effect that was reversed by restoring miR-143-3p or silencing the Hedgehog inhibitor HHIP. The identification of lncRNA-mediated crosstalk between VSMCs and endothelial cells in PAD pathophysiology reveals possible therapeutic targets for CLTI and underscores the translational potential of RNA-based strategies in ischemic vascular disease.<\/jats:p>","DOI":"10.1172\/jci197708","type":"journal-article","created":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T19:53:39Z","timestamp":1760471619000},"source":"Crossref","is-referenced-by-count":1,"title":["CARMN orchestrates angiogenesis from behind the opera scenes: signing love letters to the endothelium"],"prefix":"10.1172","volume":"135","author":[{"given":"Shivangi","family":"Pande","sequence":"first","affiliation":[{"name":"Department of Medicine, Wilf Family Cardiovascular Research Institute, Einstein-Mount Sinai Diabetes Research Center (ES-DRC), Fleischer Institute for Diabetes and Metabolism (FIDAM), Albert Einstein College of Medicine, New York, New York, 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