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论文题目
Antipsychotic drugs induce vascular defects in hematopoietic organs
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作者
Deng Zhao-Hua, Zhong Jing, Jiang Hai-Lin, Jeong Hyun-Woo, Chen Jian-Wei, Shu Ya-Hai, Tan Ming, Adams Ralf H, Xie Ke-Ping, Chen Qi, Liu Yang.
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论文出处
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刊物名称
FASEB Journal
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年卷期页
2022, 36, 10, e22538
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联系作者
Qi Chen
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影响因子
5.834
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摘要
Antipsychotic agents are clinically utilized to treat schizophrenia and other mental disorders. These drugs induce neurological and metabolic side effects, but their influence on blood vessels remains largely unknown. Here, we show that haloperidol, one of the most frequently prescribed antipsychotic agents, induces vascular defects in bone marrow. Acute haloperidol treatment results in vascular dilation that is specific to hematopoietic organs. This vessel dilation is associated with disruption of hematopoiesis and hematopoietic stem/progenitor cells (HSPCs), both of which are reversible after haloperidol withdrawal. Mechanistically, haloperidol treatment blocked the secretion of vascular endothelial growth factor A (VEGF-A) from HSPCs. Genetic blockade of VEGF-A secretion from hematopoietic cells or inhibition of VEGFR2 in endothelial cells result in similar vessel dilation in bone marrow during regeneration after irradiation and transplantation. Conversely, VEGF-A gain of function rescues the bone marrow vascular defects induced by haloperidol treatment and irradiation. Our work reveals an unknown effect of antipsychotic agents on the vasculature and hematopoiesis with potential implications for drug application in clinic.
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英文摘要
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外单位作者单位
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