Long noncoding RNA SRRM2-AS1 mediates coronary artery damage in Kawasaki disease by promoting endothelial-to-mesenchymal transition

Kawasaki disease (KD) is the leading cause of acquired heart disease in children, though its etiology and underlying mechanisms remain elusive. Emerging evidence indicates that long noncoding RNAs (lncRNAs) regulate endothelial-to-mesenchymal transition (EndMT), a cellular process implicated in vascular pathology. However, the specific involvement of lncRNAs in KD-associated coronary artery damage via EndMT remains undefined. Here, we show that the lncRNA SRRM2-AS1 is markedly elevated in the serum of children with KD and is internalized by coronary artery endothelial cells. Overexpression of SRRM2-AS1 in human coronary artery endothelial cells (HCAECs) increased cell migration and induced EndMT, as confirmed by elevated mesenchymal marker expression and morphological changes. Mechanistically, bioinformatics analysis, dual-luciferase reporter assays, and gene expression profiling revealed SRRM2 as a direct target of SRRM2-AS1. Our findings suggest that SRRM2 promotes EndMT through ubiquitin C (UBC) and the PI3K/Akt/GSK-3β/β-catenin signaling pathway. In a mouse model of KD, recombinant AAV9-mediated SRRM2-AS1 overexpression intensified coronary artery inflammation and increased vimentin expression, further supporting its role in EndMT. Collectively, these results demonstrate that SRRM2-AS1 drives EndMT in KD via the SRRM2/UBC/PI3K/Akt/GSK-3β/β-catenin axis, thereby contributing to coronary artery damage. Consequently, SRRM2-AS1 emerges as a promising therapeutic target for KD-associated vasculopathy, offering potential avenues to mitigate cardiovascular complications in affected children.