title: Inhibition of autophagy ameliorates pulmonary microvascular dilation and PMVECs excessive proliferation in rat experimental hepatopulmonary syndrome.
abstract: Hepatopulmonary syndrome (HPS) is a defective liver-induced pulmonary vascular disorder with massive pulmonary microvascular dilation and excessive proliferation of pulmonary microvascular endothelial cells (PMVECs). Growing evidence suggests that autophagy is involved in pulmonary diseases, protectively or detrimentally. Thus, it is interesting and important to explore whether autophagy might be involved in and critical in HPS. In the present study, we report that autophagy was activated in common bile duct ligation (CBDL) rats and cultured pulmonary PMVECs induced by CBDL rat serum, two accepted in vivo and in vitro experimental models of HPS. Furthermore, pharmacological inhibition of autophagy with 3-methyladenine (3-MA) significantly alleviated pathological alterations and typical symptom of HPS in CBDL rats in vivo, and consistently 3-MA significantly attenuated the CBDL rat serum-induced excessive proliferation of PMVECs in vitro. All these changes mediated by 3-MA might explain the observed prominent improvement of pulmonary appearance, edema, microvascular dilatation and arterial oxygenation in vivo. Collectively, these results suggest that autophagy activation may play a critical role in the pathogenesis of HPS, and autophagy inhibition may have a therapeutic potential for this disease.
authors.affiliation: Department of Anesthesia, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Duo
authors.initials: D
authors.lastname: Xu
authors.affiliation: Department of Anesthesia, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Chen
authors.affiliation: Department of Anesthesia, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Jianteng
authors.initials: J
authors.lastname: Gu
authors.affiliation: Department of Anesthesia, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Chen
authors.affiliation: University P. Sabatier Toulouse 3 and CNRS, LBCMCP, 31062 Toulouse Cedex 9, France.
authors.forename: Karine
authors.initials: K
authors.lastname: Belguise
authors.affiliation: University P. Sabatier Toulouse 3 and CNRS, LBCMCP, 31062 Toulouse Cedex 9, France.
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Anesthesia, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Yi
authors.affiliation: Department of Anesthesia, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Kaizhi
authors.initials: K
authors.lastname: Lu
mesh_terms: D000818:Animals; D001343:Autophagy; D049109:Cell Proliferation; D002478:Cells, Cultured; D003135:Common Bile Duct / Q000601:surgery*; D004106:Dilatation; D004730:Endothelium, Vascular / Q000473:pathology*; D020065:Hepatopulmonary Syndrome / Q000209:etiology / Q000473:pathology*; D008026:Ligation / Q000009:adverse effects; D008297:Male; D011651:Pulmonary Artery / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley