Endothelial Cell Integrin α6 Regulates Vascular Remodeling Through the PI3K/Akt-eNOS-VEGFA Axis After Stroke.
10.1007/s12264-025-01403-6
- Author:
Bing-Qiao WANG
1
;
Yang-Ying DUAN
2
;
Mao CHEN
1
;
Yu-Fan MA
1
;
Ru CHEN
1
;
Cheng HUANG
1
;
Fei GAO
1
;
Rui XU
3
;
Chun-Mei DUAN
4
Author Information
1. 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.
3. Department of Neurology, Xinqiao Hospital, The Army Medical University, Chongqing, 400037, China. xurui007@tmmu.edu.cn.
4. Department of Neurology, Xinqiao Hospital, The Army Medical University, Chongqing, 400037, China. duancm0629@tmmu.edu.cn.
- Publication Type:Journal Article
- Keywords:
Angiogenesis;
Integrin α6;
Ischemia
- MeSH:
Animals;
Nitric Oxide Synthase Type III/metabolism*;
Mice;
Proto-Oncogene Proteins c-akt/metabolism*;
Integrin alpha6/genetics*;
Endothelial Cells/metabolism*;
Phosphatidylinositol 3-Kinases/metabolism*;
Stroke/pathology*;
Vascular Remodeling/physiology*;
Vascular Endothelial Growth Factor A/metabolism*;
Mice, Knockout;
Signal Transduction/physiology*;
Mice, Inbred C57BL;
Male;
Neovascularization, Physiologic/physiology*
- From:
Neuroscience Bulletin
2025;41(9):1522-1536
- CountryChina
- Language:English
-
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.
