title: Danshen-Enhanced Cardioprotective Effect of Cardioplegia on Ischemia Reperfusion Injury in a Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes Model.
abstract: Myocardial ischemia-reperfusion (I/R) injury is unavoidable during cardioplegic arrest and open-heart surgery. Danshen is one of the most popular traditional herbal medicines in China, which has entered the Food and Drug Administration-approved phase III clinical trial. This study was aimed to develop a human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) model to mimic I/R injury and evaluate the cardioprotective effect of regular cardioplegic solution with Danshen. hiPSC-CMs were cultured with the crystalloid cardioplegic solution (Thomas group) and Thomas solution with 2 or 10 µg/mL Danshen (Thomas plus Danshen groups). The cells under normoxic culture condition served as baseline group. Then, the cells were placed in a modular incubator chamber. After 45 min hypoxia and 3 h reoxygenation, hiPSC-CMs subjected to hypoxia/reoxygenation resulted in a sharp increase of reactive oxygen species (ROS) content in Thomas group versus baseline group. Compared with the Thomas group, ROS accumulation was significant suppressed in Thomas plus Danshen groups, which might result from elevating the content of glutathione and enhanced activities of superoxide dismutase and glutathione peroxidase. The enhanced L-type Ca2+current in hiPSC-CMs after I/R injury was also significantly decreased by Danshen, and meanwhile intracellular Ca2+level was reduced and calcium overload was suppressed. Thomas plus Danshen groups also presented less irregular transients and lower apoptosis rates. As a result, Danshen could improve antioxidant and calcium handling in cardiomyocytes during I/R and lead to reduced arrhythmia events and apoptosis rates. hiPSC-CMs model offered a platform for the future translational study of the cardioplegia.
authors.affiliation: State Key Laboratory for Cardiovascular Diseases, Center for Pediatric Cardiac Surgery, Key Laboratory of Cardiac Regenerative Medicine, National Center for Cardiovascular Diseases and Fuwai Hospital, Beijing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
authors.affiliation: State Key Laboratory for Cardiovascular Diseases, Center for Pediatric Cardiac Surgery, Key Laboratory of Cardiac Regenerative Medicine, National Center for Cardiovascular Diseases and Fuwai Hospital, Beijing, China.
authors.forename: Yiwei
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine, Peking University, Beijing, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine, Peking University, Beijing, China.
authors.forename: Yangming
authors.initials: Y
authors.lastname: Wang
authors.affiliation: State Key Laboratory for Cardiovascular Diseases, Center for Pediatric Cardiac Surgery, Key Laboratory of Cardiac Regenerative Medicine, National Center for Cardiovascular Diseases and Fuwai Hospital, Beijing, China.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Zhang
authors.affiliation: State Key Laboratory for Cardiovascular Diseases, Center for Pediatric Cardiac Surgery, Key Laboratory of Cardiac Regenerative Medicine, National Center for Cardiovascular Diseases and Fuwai Hospital, Beijing, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002314:Cardioplegic Solutions / Q000494:pharmacology*; D002316:Cardiotonic Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D006324:Heart Arrest, Induced / Q000379:methods*; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D027561:Salvia miltiorrhiza / Q000737:chemistry
chemical_list: D002314:Cardioplegic Solutions; D002316:Cardiotonic Agents; D004365:Drugs, Chinese Herbal; C028972:dan-shen root extract; D002118:Calcium
keywords: -Cardiomyocyte; -Cardioplegia; -Ischemia/reperfusion; Induced pluripotent stem cells