title: Cytoprotective Role of Alpha-1 Antitrypsin in Vascular Endothelial Cell Under Hypoxia/Reoxygenation Condition.
abstract: Ischemia/reperfusion (IR) injury is a critical factor in the pathogenesis of tissue injury after myocardial infarction, multiple organ failure, and other acute ischemic events. Previous studies suggest that α1-antitrypsin (AAT) plays a cytoprotective role in beta cells and human pulmonary cells. We hypothesize that AAT may have the potential to reduce IR-induced vascular injury involved in cell apoptosis and permeability. In this study, we investigate the role of AAT in human umbilical vein endothelial cells using a model wherein endothelial cell monolayers are exposed to hypoxia/reoxygenation (HR). We found that exogenous AAT alleviated HR injury in a dose- and time-dependent manner. Furthermore, by gain and loss function experiments, we demonstrated that overexpression of AAT decreased cell apoptosis and promoted proliferation by inhibiting Rac1/PAK/p38 signaling and against oxidative stress, and also reduced cellular permeability by increasing ZO-1 and occludin expression. Thus, we provided evidences to illustrate that AAT played a cytoprotective role in vascular endothelial cell under HR condition, suggesting that AAT treatment may be therapeutically beneficial to reduce IR-induced vascular injury.
authors: Department of Obstetrics and Gynecology, Wuxi Maternal and Child Health Hospital Affiliated to Nanjing Medical University, Wuxi, China.
authors: Yaling
authors: Y
authors: Feng
authors: Lingqing
authors: L
authors: Hu
authors: Qian
authors: Q
authors: Xu
authors: Hua
authors: H
authors: Yuan
authors: Linlin
authors: L
authors: Ba
authors: Yue
authors: Y
authors: He
authors: Haisha
authors: H
authors: Che
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D015687:Cell Hypoxia / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D019610:Cytoprotection / Q000187:drug effects* / Q000502:physiology*; D042783:Endothelial Cells / Q000187:drug effects* / Q000502:physiology*; D057809:HEK293 Cells; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D000515:alpha 1-Antitrypsin / Q000494:pharmacology*
chemical_list: D000515:alpha 1-Antitrypsin