Blood-brain barrier(BBB)dysfunction represents a critical pathological manifestation in exacerbating ischemic stroke,contributing to neuronal death,edema formation,and unfavorable clinical outcomes.GATA zinc finger do...Blood-brain barrier(BBB)dysfunction represents a critical pathological manifestation in exacerbating ischemic stroke,contributing to neuronal death,edema formation,and unfavorable clinical outcomes.GATA zinc finger domain-containing 1(GATAD1)is recognized as a critical transcription factor in cardiac development and cardiovascular disease.However,the role of GATAD1 in regulating BBB function and ischemic stroke remains elusive.Here,we found that GATAD1 was upregulated in cerebral endothelial cells(ECs)following ischemic stroke in mice.EC-specific Gatad1 deficiency demonstrated remarkable neuroprotection,manifested by reduced infarct volumes,ameliorated BBB dysfunction,and improved neurological outcomes following experimental stroke.Mechanistic investigations revealed that GATAD1 was involved in regulating CD36 expression,thereby modulating caveolae-mediated transcytosis in cerebral ECs.These findings established GATAD1 as a novel regulator of BBB permeability and a potential therapeutic target for ischemic stroke intervention.展开更多
基金Natural Science Foundation of China(82101425,82130036)Jiangsu Innovative and Entrepreneurial Talent Program(JSSCBS20211497)+2 种基金STI2030-Major Projects(2022ZD0211800)Jiangsu Province Key Medical Discipline(ZDXK202216)Healthcare Research Project for Cadres of Jiangsu Province(BJ20002)。
文摘Blood-brain barrier(BBB)dysfunction represents a critical pathological manifestation in exacerbating ischemic stroke,contributing to neuronal death,edema formation,and unfavorable clinical outcomes.GATA zinc finger domain-containing 1(GATAD1)is recognized as a critical transcription factor in cardiac development and cardiovascular disease.However,the role of GATAD1 in regulating BBB function and ischemic stroke remains elusive.Here,we found that GATAD1 was upregulated in cerebral endothelial cells(ECs)following ischemic stroke in mice.EC-specific Gatad1 deficiency demonstrated remarkable neuroprotection,manifested by reduced infarct volumes,ameliorated BBB dysfunction,and improved neurological outcomes following experimental stroke.Mechanistic investigations revealed that GATAD1 was involved in regulating CD36 expression,thereby modulating caveolae-mediated transcytosis in cerebral ECs.These findings established GATAD1 as a novel regulator of BBB permeability and a potential therapeutic target for ischemic stroke intervention.
