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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\u2010A) from HSPCs. Genetic blockade of VEGF\u2010A 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\u2010A 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.<\/jats:p>","DOI":"10.1096\/fj.202200862r","type":"journal-article","created":{"date-parts":[[2022,9,6]],"date-time":"2022-09-06T03:42:12Z","timestamp":1662435732000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Antipsychotic drugs induce vascular defects in hematopoietic organs"],"prefix":"10.1096","volume":"36","author":[{"given":"Zhao\u2010hua","family":"Deng","sequence":"first","affiliation":[{"name":"Center for cell lineage and development, CAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine | GIBH\u2010HKU Guangdong\u2010Hong Kong Stem Cell and Regenerative Medicine Research Centre | GIBH\u2010CUHK Joint Research Laboratory on Stem Cell and Regenerative Medicine Guangzhou Institutes of 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GIBH\u2010CUHK Joint Research Laboratory on Stem Cell and Regenerative Medicine Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences  Guangzhou China"},{"name":"China\u2010New Zealand Joint Laboratory on Biomedicine and Health  Guangzhou China"},{"name":"Institutes of Physical Science and Information Technology Anhui University  Hefei China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ya\u2010hai","family":"Shu","sequence":"additional","affiliation":[{"name":"Center for cell lineage and development, CAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine | GIBH\u2010HKU Guangdong\u2010Hong Kong Stem Cell and Regenerative Medicine Research Centre | GIBH\u2010CUHK Joint Research Laboratory on Stem Cell and Regenerative Medicine Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences  Guangzhou China"},{"name":"China\u2010New Zealand Joint Laboratory on Biomedicine 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