title: Crosstalk between ACE2 and PLGF regulates vascular permeability during acute lung injury.
abstract: 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 placental growth factor (PLGF) remain ill-defined. In the current study, we examined the relationship between ACE2 and PLGF in ALI model in mice. We used a previously published bleomycin method to induce ALI in mice, and treated the mice with ACE2. We analyzed the levels of PLGF in these mice. The mouse lung vessel permeability was determined by a fluorescence pharmacokinetic assay following i.v. injection of 62.5 µg/kg Visudyne. PLGF pump or soluble Flt-1 (sFlt-1) pump was given to augment or suppress PLGF effects, respectively. The long-term effects on lung function were determined by measurement of lung resistance using methacholine. We found that ACE2 treatment did not alter PLGF levels in lung, but antagonized the effects of PLGF on increases of lung vessel permeability. Ectogenic PLGF abolished the antagonizing effects of ACE2 on the vessel permeability against PLGF. On the other hand, suppression of PLGF signaling mimicked the effects of ACE2 on the vessel permeability against PLGF. The suppression of vessel permeability resulted in improvement of lung function after ALI. Thus, ACE2 may antagonize the PLGF-mediated increases in lung vessel permeability during ALI, resulting in improvement of lung function after ALI.
authors.affiliation: Department of Emergency, Fourth Hospital of Hebei Medical University Shijiazhuang 050011, China.
authors.forename: Lantao
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Surgery, Fourth Hospital of Hebei Medical University Shijiazhuang 050011, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Emergency, Fourth Hospital of Hebei Medical University Shijiazhuang 050011, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Qin
authors.affiliation: Department of Emergency, Fourth Hospital of Hebei Medical University Shijiazhuang 050011, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Xing
authors.affiliation: Department of Emergency, Fourth Hospital of Hebei Medical University Shijiazhuang 050011, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Su
authors.affiliation: Department of Emergency, Fourth Hospital of Hebei Medical University Shijiazhuang 050011, China.
authors.forename: Zhenjie
authors.initials: Z
authors.lastname: Hu
keywords: Acute lung injury (ALI); angiotensin converting enzyme 2 (ACE2); placental growth factor (PLGF); vessel permeability