title: Acetylated cyclophilin A is a major mediator in hypoxia-induced autophagy and pulmonary vascular angiogenesis.
abstract: Autophagy is a major intracellular degradation and recycling process that maintains cellular homeostasis, which is involved in structural and functional abnormalities of pulmonary vasculature in hypoxic pulmonary arterial hypertension (HPAH). Cyclophilin A (CyPA) is a secreted, oxidative stress-induced factor. Its role in inducing autophagy and augmenting endothelial cell dysfunction has never been explored.
  
  
  
  Lungs from rats exposed to chronic hypoxia were examined for autophagy with electron microscopy, western blotting, and fluorescence microscopy.
  
  
  
  Activated autophagy was seen in the endothelium of the pulmonary artery from experimental rat models of HPAH and cultured bovine pulmonary arterial endothelial cells under hypoxia. Inhibiting autophagy attenuated the pathological progression of HPAH and repressed endothelial cell migration and angiogenesis. We also showed that CyPA was upregulated and acetylated under hypoxia and led to the abnormal occurrence of autophagy through its interaction with autophagy protein 5 and autophagy protein 7. Moreover, acetylated CyPA was essential for the excessive proliferation, migration, and tube formation networks of pulmonary arterial endothelial cells.
  
  
  
  Our results indicate the crucial role of acetylated CyPA in the abnormal occurrence of autophagy and subsequent pulmonary vascular angiogenesis.
authors.affiliation: aDepartment of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University, Daqing bBiopharmaceutical Key Laboratory of Heilongjiang Province, Harbin cDepartment of Pharmaceutical Analysis, College of Pharmacy, Harbin Medical University, Harbin, Heilongjiang Province dDepartment of Pathophysiology, College of Basic Medicine, Harbin Medical University, Daqing, China.
authors.forename: Min
authors.initials: M
authors.lastname: Mao
authors.forename: Xiufeng
authors.initials: X
authors.lastname: Yu
authors.forename: Xin
authors.initials: X
authors.lastname: Ge
authors.forename: Rui
authors.initials: R
authors.lastname: Gu
authors.forename: Qian
authors.initials: Q
authors.lastname: Li
authors.forename: Shasha
authors.initials: S
authors.lastname: Song
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Zheng
authors.forename: Tingting
authors.initials: T
authors.lastname: Shen
authors.forename: Xuecang
authors.initials: X
authors.lastname: Li
authors.forename: Yao
authors.initials: Y
authors.lastname: Fu
authors.forename: Jiali
authors.initials: J
authors.lastname: Li
authors.forename: Daling
authors.initials: D
authors.lastname: Zhu
mesh_terms: D000107:Acetylation; D000818:Animals; D001343:Autophagy; D000071187:Autophagy-Related Protein 5 / Q000378:metabolism; D000071193:Autophagy-Related Protein 7 / Q000378:metabolism; D002417:Cattle; D002465:Cell Movement; D002478:Cells, Cultured; D021984:Cyclophilin A / Q000378:metabolism*; D019610:Cytoprotection; D042783:Endothelial Cells / Q000378:metabolism; D004727:Endothelium / Q000378:metabolism / Q000503:physiopathology*; D006976:Hypertension, Pulmonary / Q000378:metabolism* / Q000503:physiopathology; D000860:Hypoxia / Q000503:physiopathology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D011651:Pulmonary Artery; D051381:Rats
chemical_list: D000071187:Autophagy-Related Protein 5; D021984:Cyclophilin A; D000071193:Autophagy-Related Protein 7