Endothelial Cell Integrin α6 Regulates Vascular Remodeling Through the PI3K/Akt-eNOS-VEGFA Axis After Stroke
Bing‑Qiao Wang1 · Yang‑Ying Duan2 · Mao Chen1 · Yu‑Fan Ma1 · Ru Chen1 · Cheng Huang1 · Fei Gao1 · Rui Xu1 · Chun‑Mei Duan11 Department of Neurology, Xinqiao Hospital, The Army Medical University, Chongqing 400037, China
2 Department of Ultrasound Medicine, Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, China
Abstract
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.
Keywords
Integrin α6; Ischemia; Angiogenesis
