title: Atorvastatin Inhibits Myocardial Apoptosis in a Swine Model of Coronary Microembolization by Regulating PTEN/PI3K/Akt Signaling Pathway.
abstract: OBJECTIVE
  Phosphatase and tensin homolog deleted on chromosome ten (PTEN) has been recognized as a promoter of apoptosis in various tissues, and revealed to be up-regulated in circumstances of coronary microembolization (CME). However, whether this functional protein could be modified by pretreatment of atorvastatin in models of CME has not been disclosed yet.
  
  
  METHODS
  Swine CME was induced by intra-coronary injection of inertia plastic microspheres (diameter 42 μm) into left anterior descending coronary, with or without pretreatment of atorvastatin or PTEN siRNA. Echocardiologic measurements, pathologic examination, TUNEL staining and western blotting were applied to assess their functional, morphological and molecular effects in CME.
  
  
  RESULTS
  PTEN were aberrantly up-regulated in cardiomyocytes following CME, with both the mRNA and protein levels increased after CME modeling. Pretreatment with atorvastatin could attenuate the induction of PTEN. Furthermore, down-regulation of PTEN in vivo via siRNA was associated with an improved cardiac function, attenuated myocardial apoptosis, and concomitantly inhibited expressions of key proapoptotic proteins such as Bax, cleaved-caspase-3. Interestingly, atorvastatin could markedly attenuate PTEN expression and therefore partially reverse cardiac dysfunction and attenuate the apoptosis of the myocardium following CME.
  
  
  CONCLUSIONS
  Modulation of PTEN was probably as a potential mechanism involved in the beneficial effects of pretreatment of atorvastatin to cardiac function and apoptosis in large animal models of CME.
authors.affiliation: Department of Cardiology, the First Affiliated Hospital of Guangxi Medical University, Guangxi Cardiovascular Institute, Nanning, China.
authors.forename: Jiangyou
authors.initials: J
authors.lastname: Wang
authors.forename: Han
authors.initials: H
authors.lastname: Chen
authors.forename: You
authors.initials: Y
authors.lastname: Zhou
authors.forename: Qiang
authors.initials: Q
authors.lastname: Su
authors.forename: Tao
authors.initials: T
authors.lastname: Liu
authors.forename: Xian-tao
authors.initials: XT
authors.lastname: Wang
authors.forename: Lang
authors.initials: L
authors.lastname: Li
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D000069059:Atorvastatin / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D004195:Disease Models, Animal; D015536:Down-Regulation; D004452:Echocardiography; D004617:Embolism / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D009203:Myocardial Infarction / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D051059:PTEN Phosphohydrolase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013552:Swine; D019210:Troponin I / Q000097:blood; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D034741:RNA, Small Interfering; D019210:Troponin I; D051028:bcl-2-Associated X Protein; D000069059:Atorvastatin; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; D053148:Caspase 3