Wang Bing-Qiao, Duan Yang-Ying, Chen Mao, Ma Yu-Fan, Chen Ru, Huang Cheng, Gao Fei, Xu Rui, Duan Chun-Mei
Department of Neurology, Xinqiao Hospital, The Army Medical University, Chongqing, 400037, China.
Department of Ultrasound Medicine, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610072, China.
Neurosci Bull. 2025 May 2. doi: 10.1007/s12264-025-01403-6.
The angiogenic response is essential for the repair of ischemic brain tissue. Integrin α6 (Itga6) expression has been shown to increase under hypoxic conditions and is expressed exclusively in vascular structures; however, its role in post-ischemic angiogenesis remains poorly understood. In this study, we demonstrate that mice with endothelial cell-specific knockout of Itga6 exhibit reduced neovascularization, reduced pericyte coverage on microvessels, and accelerated breakdown of microvascular integrity in the peri-infarct area. In vitro, endothelial cells with ITGA6 knockdown display reduced proliferation, migration, and tube-formation. Mechanistically, we demonstrated that ITGA6 regulates post-stroke angiogenesis through the PI3K/Akt-eNOS-VEGFA axis. Importantly, the specific overexpression of Itga6 in endothelial cells significantly enhanced neovascularization and enhanced the integrity of microvessels, leading to improved functional recovery. Our results suggest that endothelial cell Itga6 plays a crucial role in key steps of post-stroke angiogenesis, and may represent a promising therapeutic target for promoting recovery after stroke.
血管生成反应对于缺血性脑组织的修复至关重要。整合素α6（Itga6）的表达已被证明在缺氧条件下会增加，并且仅在血管结构中表达；然而，其在缺血后血管生成中的作用仍知之甚少。在本研究中，我们证明内皮细胞特异性敲除Itga6的小鼠表现出新生血管形成减少、微血管周围周细胞覆盖减少以及梗死周围区域微血管完整性加速破坏。在体外，ITGA6敲低的内皮细胞显示出增殖、迁移和管形成减少。从机制上讲，我们证明ITGA6通过PI3K/Akt-eNOS-VEGFA轴调节中风后血管生成。重要的是，内皮细胞中Itga6的特异性过表达显著增强了新生血管形成并增强了微血管的完整性，从而导致功能恢复改善。我们的结果表明，内皮细胞Itga6在中风后血管生成的关键步骤中起关键作用，并且可能代表促进中风后恢复的有希望的治疗靶点。
