title: Astragalus polysaccharide protects human cardiac microvascular endothelial cells from hypoxia/reoxygenation injury: The role of PI3K/AKT, Bax/Bcl-2 and caspase-3.
abstract: In the present study, the mechanisms associated with the Astragalus polysaccharide (APS)-mediated protection of human cardiac microvascular endothelial cells (HCMEC) against hypoxia/reoxygenation (HR) injury were investigated. Pretreatment of HCMECs with APS at various concentrations was performed prior to Na2S2O4-induced HR injury. Subsequently, cell viability and apoptosis were measured by MTT and Hoechst assays, respectively. The viability of HCMECs was reduced by Na2S2O4 and apoptosis was enhanced; however, cell viability was observed to be increased by APS via inhibition of apoptosis. Additionally, intracellular reactive oxygen species (ROS), Ca2+, nitric oxide (NO), malondialdehyde (MDA), superoxide dismutase (SOD), phosphatidylinositol 3-kinase (PI3K)-protein kinase B (AKT), B‑cell lymphoma‑2 (Bcl‑2), Bcl‑2 associated X protein (Bax) and caspase‑3 were measured using detection kits or western blot analysis. In HCMECs with HR injury, the levels of ROS and Ca2+, MDA and Bax expression levels, and the activity of caspase‑3 were elevated. By contrast, the level of NO, the protein expression levels of SOD, Bcl‑2 and PI3K, and the phosphorylation of AKT were decreased. However, compared with the HR group, the effects of HR injury were significantly reduced by APS, with APS providing a protective effect on HCMECs, particularly at higher doses. The current study concluded that APS protects HCMECs from Na2S2O4‑induced HR injury by reducing the levels of ROS, Ca2+, MDA and Bax, inhibiting the activity of caspase‑3, and enhancing the levels of NO, SOD, Bcl‑2, PI3K and phosphorylated AKT. These results may provide an insight into the clinical application of APS and novel therapeutic strategies for HR injury.
authors.affiliation: Department of Cardiology, Dongfang Hospital of Beijing University of Chinese Medicine, Beijing 100078, P.R. China.
authors.forename: Liandi
authors.initials: L
authors.lastname: Xie
authors.affiliation: Department of Cardiology, Dongfang Hospital of Beijing University of Chinese Medicine, Beijing 100078, P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Cardiology, Dongfang Hospital of Beijing University of Chinese Medicine, Beijing 100078, P.R. China.
authors.forename: Zongjing
authors.initials: Z
authors.lastname: Fan
authors.affiliation: Department of Cardiology, Dongfang Hospital of Beijing University of Chinese Medicine, Beijing 100078, P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Cardiology, Beijing University of Chinese Medicine, Beijing 100029, P.R. China.
authors.forename: Jixiang
authors.initials: J
authors.lastname: Zeng
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D027883:Astragalus Plant / Q000737:chemistry*; D002118:Calcium / Q000378:metabolism; D002316:Cardiotonic Agents / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D000860:Hypoxia / Q000378:metabolism*; D008315:Malondialdehyde / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D010084:Oxidation-Reduction; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D011134:Polysaccharides / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000378:metabolism* / Q000473:pathology; D013482:Superoxide Dismutase / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D002316:Cardiotonic Agents; D011134:Polysaccharides; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D051028:bcl-2-Associated X Protein; D009569:Nitric Oxide; D008315:Malondialdehyde; D013482:Superoxide Dismutase; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt; D053148:Caspase 3; D002118:Calcium