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. 2025 Sep;41(9):1522-1536.
doi: 10.1007/s12264-025-01403-6. Epub 2025 May 2.

Endothelial Cell Integrin α6 Regulates Vascular Remodeling Through the PI3K/Akt-eNOS-VEGFA Axis After Stroke

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
Affiliations

Endothelial Cell Integrin α6 Regulates Vascular Remodeling Through the PI3K/Akt-eNOS-VEGFA Axis After Stroke

Bing-Qiao Wang et al. Neurosci Bull. 2025 Sep.

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: Angiogenesis; Integrin α6; Ischemia.

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Conflict of interest statement

Conflict of interest: The authors declare that there is no conflict of interest in the research, authorship, or publication of this article.

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