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;howeve...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.展开更多
基金supported by grants from the Scientific Research Foundation for Young Doctors of the Second Affiliated Hospital,Army Medical University(2022YQB041)the Chongqing Natural Science Foundation(CSTB2024NSCQ-MSX0924 and CSTB2024NSCQ-MSX0909).
文摘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.
