Vascular repair is considered a key restorative measure to improve long-term outcomes after ischemic stroke. N⁶-methyladenosine (m⁶A), the most prevalent internal modification in eukaryotic mRNAs, functionally mediates vascular repair. However, whether circular RNA SCMH1 (circSCMH1) promotes vascular repair by m⁶A methylation after stroke remains to be elucidated. Here, we identify the role of circSCMH1 in promoting vascular repair in peri-infarct cortex of male mice and male monkeys after photothrombotic (PT) stroke, and attenuating the ischemia-induced m⁶A methylation in peri-infarct cortex of male mice after PT stroke. Mechanically, circSCMH1 increased the translocation of ubiquitination-modified fat mass and obesity-associated protein (FTO) into nucleus of endothelial cells (ECs), leading to m⁶A demethylation of phospholipid phosphatase 3 (Plpp3) mRNA and subsequently the increase of Plpp3 expression in ECs. Our data demonstrate that circSCMH1 enhances vascular repair via FTO-regulated m⁶A methylation after stroke, providing insights into the mechanism of circSCMH1 in promoting stroke recovery.

血管修复被认为是改善缺血性中风后长期结果的关键恢复措施。N ⁶ -甲基腺苷 (m ⁶ A) 是真核 mRNA 中最普遍的内部修饰，在功能上介导血管修复。然而，环状 RNA SCMH1 (circSCMH1) 是否通过 m ⁶ A 甲基化在卒中后促进血管修复仍有待阐明。^{在这里，我们确定了 circSCMH1 在促进光血栓形成 (PT) 卒中后雄性小鼠和雄性猴梗死周围皮层血管修复以及减轻缺血诱导的 m 6}中的作用PT 中风后雄性小鼠梗塞周围皮质的甲基化。从机械上讲，circSCMH1 增加了泛素化修饰的脂肪量和肥胖相关蛋白 (FTO) 向内皮细胞 (EC) 细胞核的易位，导致磷脂磷酸酶 3 (Plpp3) mRNA 的 m 6 A 去甲基化，随后^增加了Plpp3表达在 EC 中。我们的数据表明，circSCMH1 通过中风后FTO 调节的 m ⁶ A 甲基化增强血管修复，从而深入了解 circSCMH1 促进中风恢复的机制。