title: The PTEN/Akt Signaling Pathway Mediates Myocardial Apoptosis in Swine After Coronary Microembolization.
abstract: Phosphatase and the tensin homolog deleted on chromosome ten (PTEN) has been recognized as a promoter of apoptosis in various tissues and has been shown to be upregulated in circumstances of coronary microembolization (CME). We hypothesized that the upregulation of PTEN correlates with CME-induced myocardial apoptosis.
  
  
  
  Swine CME was induced by an intracoronary injection of inert plastic microspheres (diameter of 42 μm) into the left anterior descending coronary, with or without pretreatment of the PTEN small-interfering RNA (siRNA). Echocardiological measurements, a pathological examination, Terminal-deoxynucleoitidyl Transferase Mediated Nick End Labeling (TUNEL) staining, and Western blotting, were performed to assess their functional, morphological, and molecular effects in CME.
  
  
  
  PTEN was aberrantly upregulated in cardiomyocytes following CME. Downregulation of PTEN in vivo via siRNA was associated with improved cardiac function and attenuated myocardial apoptosis; concomitantly inhibited the expression of key proapoptotic proteins, such as phosphorylated Bad (p-Bad); cleaved caspase-3; and enhanced the expression of key antiapoptotic proteins, such as phosphorylated protein kinase B (p-Akt). However, there was no difference in the Akt-regulated downstream protein IκB kinases (IKKα, IKKβ, and IKKγ) among the sham, CME, and control siRNA groups.
  
  
  
  This study demonstrates, for the first time, that the PTEN/Akt signaling pathway contributes to cardiomyocyte apoptosis. The data generated from this study provide a rationale for the development of PTEN-based therapeutic strategies for CME-induced myocardial injury.
authors: Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
authors: Jiangyou
authors: J
authors: Wang
authors: Department of Cardiac Surgery, Wuhan Asia Heart Hospital in China, Wuhan, China.
authors: Han
authors: H
authors: Chen
authors: Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
authors: Qiang
authors: Q
authors: Su
authors: Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
authors: You
authors: Y
authors: Zhou
authors: Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
authors: Tao
authors: T
authors: Liu
authors: Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China drlilang@163.com.
authors: Lang
authors: L
authors: Li
mesh_terms: D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D003324:Coronary Artery Disease / Q000201:enzymology* / Q000235:genetics / Q000473:pathology / Q000628:therapy; D004195:Disease Models, Animal; D004617:Embolism / Q000201:enzymology* / Q000235:genetics / Q000473:pathology / Q000628:therapy; D015971:Gene Expression Regulation, Enzymologic; D009206:Myocardium / Q000201:enzymology* / Q000473:pathology; D032383:Myocytes, Cardiac / Q000201:enzymology / Q000473:pathology; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D000067492:RNAi Therapeutics; D015398:Signal Transduction; D013318:Stroke Volume; D034421:Sus scrofa; D015854:Up-Regulation; D016277:Ventricular Function, Left
chemical_list: D051017:Apoptosis Regulatory Proteins; D034741:RNA, Small Interfering; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase
keywords: Akt; Bad; PTEN; apoptosis; caspase-3; coronary microembolization