title: Atorvastatin protects myocardium against ischemia-reperfusion arrhythmia by increasing Connexin 43 expression: A rat model.
abstract: Atorvastatin has protective effects against myocardial ischemia-reperfusion injuries and ischemia-reperfusion arrhythmia. This study was designed to investigate whether atorvastatin is able to protect against myocardial ischemia-reperfusion injury by enhancing the expression of Connexin 43 (Cx43) via the activation of the phosphatidylinositol-3-kinase (PI3K)/Akt pathway and mitochondrial ATP-sensitive potassium (K(ATP)) channels. Isolated perfused rat hearts were treated with classic ischemia postconditioning (IPOST), atorvastatin, and atorvastatin combined with inhibitor of PI3K and K(ATP) channels, respectively, after 30min of LAD ischemia and then subjected to reperfusion for 120min. The QRS duration and the ischemia-reperfusion ventricular arrhythmia were assessed. The lactate dehydrogenase (LDH) and creatine kinase isoenzyme (CK-MB) levels were measured and the Cx43 expression was assessed by immunoblotting and immunohistochemistry. After 120min of reperfusion, atorvastatin and IPOST significantly decreased the QRS duration and inhibited ventricular arrhythmia. They also decreased the levels of LDH and CK-MB. Meanwhile, atorvastatin and IPOST also significantly enhanced the Cx43 expression and the phosphorylation of Cx43. Such protective effects were abolished in the presence of the inhibitor of PI3K or the inhibitor of mitochondrial K(ATP) channels. This study suggests that atorvastatin protected against myocardial ischemia-reperfusion injury and enhanced the expression of Cx43 by activating the PI3K/Akt pathway and mitochondrial K(ATP) channels.
authors.affiliation: Cardiology Department, Tianjin Medical University General Hospital, Tianjin, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Bian
authors.affiliation: Cardiology Department, Tianjin Medical University General Hospital, Tianjin, China. Electronic address: tjyuxuefang@163.com.
authors.forename: Xuefang
authors.initials: X
authors.lastname: Yu
authors.affiliation: Cardiology Department, Tianjin Medical University General Hospital, Tianjin, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Cardiology Department, Tianjin Medical University General Hospital, Tianjin, China.
authors.forename: Tianming
authors.initials: T
authors.lastname: Teng
authors.affiliation: Cardiology Department, Tianjin Medical University General Hospital, Tianjin, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Nie
mesh_terms: D000818:Animals; D001145:Arrhythmias, Cardiac / Q000150:complications* / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D000069059:Atorvastatin / Q000494:pharmacology*; D018031:Connexin 43 / Q000378:metabolism*; D052279:Creatine Kinase, MB Form / Q000097:blood; D019610:Cytoprotection / Q000187:drug effects; D004195:Disease Models, Animal; D006339:Heart Rate / Q000187:drug effects; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008297:Male; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000150:complications*; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D018031:Connexin 43; D010750:Phosphoproteins; D000069059:Atorvastatin; D007770:L-Lactate Dehydrogenase; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D052279:Creatine Kinase, MB Form
keywords: Atorvastatin; Connexin 43; Ischemia–reperfusion arrhythmia; Mitochondrial ATP-sensitive potassium channels; PI3K/Akt