title: ACE2 Antagonizes VEGFa to Reduce Vascular Permeability During Acute Lung Injury.
abstract: OBJECTIVE
  Angiotensin converting enzyme 2 (ACE2) treatment suppresses the severity of acute lung injury (ALI), through antagonizing hydrolyzing angiotensin II (AngII) and the ALI-induced apoptosis of pulmonary endothelial cells. Nevertheless, the effects of ACE2 on vessel permeability and its relationship with vascular endothelial growth factor a (VEGFa) remain ill-defined. In the current study, we examined the relationship between ACE2 and VEGFa in ALI model in mice.
  
  
  METHODS
  Here, we used a previously published bleomycin method to induce ALI in mice, and treated the mice with ACE2. We analyzed the levels of VEGFa in these mice. The mouse lung vessel permeability was determined by a fluorescence pharmacokinetic assay following i.v. injection of 62.5µg/kg Visudyne. VEGFa pump or SU5416 pump was given to increase or decrease VEGFa effects, respectively. The long-term effects on lung function were determined by measurement of lung resistance using methacholine.
  
  
  RESULTS
  ACE2 treatment did not alter VEGFa levels in lung, but antagonized the effects of VEGFa on increases of lung vessel permeability. Ectogenic VEGFa abolished the antagonizing effects of ACE2 on the vessel permeability against VEGFa. On the other hand, suppression of VEGF signaling mimicked the effects of ACE2 on the vessel permeability against VEGFa. The suppression of vessel permeability resulted in improvement of lung function after ALI.
  
  
  CONCLUSIONS
  ACE2 may antagonize the VEGFa-mediated increases in lung vessel permeability during ALI, resulting in improvement of lung function after ALI.
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Yu
authors.forename: Qiang
authors.initials: Q
authors.lastname: Lin
authors.forename: Xiong
authors.initials: X
authors.lastname: Qin
authors.forename: Zheng
authors.initials: Z
authors.lastname: Ruan
authors.forename: Jianhua
authors.initials: J
authors.lastname: Zhou
authors.forename: Zhifeng
authors.initials: Z
authors.lastname: Lin
authors.forename: Yijiang
authors.initials: Y
authors.lastname: Su
authors.forename: Jian
authors.initials: J
authors.lastname: Zheng
authors.forename: Zhenwei
authors.initials: Z
authors.lastname: Liu
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced / Q000178:diet therapy* / Q000378:metabolism; D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D001761:Bleomycin / Q000009:adverse effects; D002199:Capillary Permeability / Q000187:drug effects*; D042783:Endothelial Cells; D005786:Gene Expression Regulation; D007211:Indoles / Q000008:administration & dosage / Q000494:pharmacology; D051379:Mice; D007703:Peptidyl-Dipeptidase A / Q000008:administration & dosage* / Q000494:pharmacology; D011166:Porphyrins / Q000008:administration & dosage / Q000493:pharmacokinetics; D011758:Pyrroles / Q000008:administration & dosage / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D000077362:Verteporfin
chemical_list: D007211:Indoles; D011166:Porphyrins; D011758:Pyrroles; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D000077362:Verteporfin; D001761:Bleomycin; C116890:Semaxinib; D007703:Peptidyl-Dipeptidase A; C000705328:Ace2 protein, mouse; D000085962:Angiotensin-Converting Enzyme 2