title: Protective effects of angiopoietin-like 4 on the blood-brain barrier in acute ischemic stroke treated with thrombolysis in mice.
abstract: Given the risk of blood-brain barrier damage (BBB) caused by ischemic and tissue plasminogen activator thrombolysis, the preservation of vascular integrity is important. Angiopoietin-like 4 (ANGPTL4), a protein secreted in hypoxia, is involved in the regulation of vascular permeability. We hypothesized that Angptl4 might exert a protective effect in thrombolysis through stabilizing blood-brain barrier and inhibit hyper-permeability.
  
  
  
  We investigated the role of Angptl4 in stroke using a transient focal cerebral ischemia mouse model. The treated mice were administered Angptl4 1h after the ischemic event upon reperfusion.
  
  
  
  Our results showed that Angptl4 combined with thrombolysis greatly reduced the infarct volume and consequent neurological deficit. Western blot analyses and gelatin zymography revealed that Angptl4 protected the integrity of the endothelium damaged by thrombolysis. Angptl4 inhibited the up-regulation of vascular endothelial growth factor (VEGF) in the vascular endothelium after stroke, which was suppressed by counteracting VEGFR signaling and diminishing downstream Src signaling, and led to the increased stability of junctions and improved endothelial cell barrier integrity.
  
  
  
  These findings demonstrated that Angptl4 protects the permeability of the BBB damaged by ischemic and thrombolysis. Suggested that Angptl4 might be a promising target molecule in therapies for vasoprotection after thrombolysis treatment.
authors.affiliation: Department of Neurology, Shanghai Jiao Tong University affiliated Sixth People's Hospital, Shanghai, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Shanghai Jiao Tong University affiliated Sixth People's Hospital, Shanghai, China.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Neurology, Shanghai Jiao Tong University affiliated Sixth People's Hospital, Shanghai, China.
authors.forename: Xiuli
authors.initials: X
authors.lastname: Chu
authors.affiliation: Department of Neurology, Shanghai Jiao Tong University affiliated Sixth People's Hospital, Shanghai, China.
authors.forename: Xiaoyang
authors.initials: X
authors.lastname: Yu
authors.affiliation: Department of Neurology, Shanghai Jiao Tong University affiliated Sixth People's Hospital, Shanghai, China. Electronic address: zhaoyuwu2005@126.com.
authors.forename: Yuwu
authors.initials: Y
authors.lastname: Zhao
mesh_terms: D000208:Acute Disease; D000075803:Angiopoietin-Like Protein 4; D042682:Angiopoietins / Q000378:metabolism* / Q000627:therapeutic use; D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism*; D020520:Brain Infarction / Q000188:drug therapy / Q000473:pathology; D002199:Capillary Permeability; D002546:Ischemic Attack, Transient / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D020521:Stroke / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D015912:Thrombolytic Therapy; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use*; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D000075803:Angiopoietin-Like Protein 4; D042682:Angiopoietins; C407088:Angptl4 protein, mouse; D042461:Vascular Endothelial Growth Factor A; D010959:Tissue Plasminogen Activator
keywords: Angiogenesis; Blood-brain barrier; Endothelium; Hypoxia; Neuroprotection; Thrombolysis