期刊
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY
卷 66, 期 1, 页码 96-107出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/FJC.0000000000000250
关键词
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资金
- Maternal and Child Health research project in Jiangsu province [F201422]
- Wuxi Bureau of Science and Technology Medical Technology Development Fund [CSE31N1321]
- standardized diagnosis and treatment projects research program of Medical Science and Technology Development Fund of the Medical Control Center in Wuxi City [YGZXG1408]
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 alpha 1-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.
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