Enhancer-Associated LncRNA-ITGA2 Promotes Vascular Remodeling Through ITGA2

作者：Xian Guo, Pan Hou, Sha Zhang, Qiang Xu, Mingyao Zhou, Wendong Tang, Faguang Jin, Bili Zhang, Zhifu Guo, Xianxian Zhao, Yue Wang, Junfeng Jiang, Pan Li · 发表于：Circulation Research · 年份：2025 · DOI：10.1161/circresaha.124.325443 · 被引用次数：14 · 研究领域：Cancer-related molecular mechanisms research、Angiogenesis and VEGF in Cancer、Kruppel-like factors research

BACKGROUND: The proliferation and migration of vascular smooth muscle cells (VSMCs) significantly contribute to vascular remodeling. Recent studies have suggested that enhancer-associated long noncoding RNAs (elncRNAs) play crucial roles in regulating gene expression and cell fate. However, the specific elncRNAs implicated in VSMC dysfunction and their regulatory mechanisms remain poorly understood. METHODS: This study used multiomics profiling techniques, including cleavage under targets and tagmentation (CUT&Tag), promoter capture high-throughput chromosome conformation capture, and microarray analysis, to identify long noncoding RNA (LncRNA)-ITGA2 (integrin α2) as a novel elncRNA involved in VSMC dysfunction. A carotid artery wire injury model was used to study its role in vascular remodeling in vivo. RNA sequencing and CRISPR-Cas9 gene-editing technology were employed to explore downstream targets of LncRNA-ITGA2. Chromatin immunoprecipitation sequencing, chromatin isolation by RNA purification, and RNA immunoprecipitation were performed to investigate its mechanistic role in VSMC proliferation and migration. RESULTS: LncRNA-ITGA2 was highly expressed in PDGF-BB (platelet-derived growth factor BB)-induced proliferative human VSMCs and was elevated in coronary atherosclerotic tissues from coronary artery disease patients compared to controls. Gain-of-function and loss-of-function studies suggested that LncRNA-ITGA2 markedly enhanced PDGF-BB-induced VSMC proliferation and m...