title: Hydroxytyrosol Protects against Myocardial Ischemia/Reperfusion Injury through a PI3K/Akt-Dependent Mechanism.
abstract: OBJECTIVE
  To investigate the effects and mechanisms of hydroxytyrosol (HT) during the pathogenesis of myocardial ischemia reperfusion (I/R) in rat hearts.
  
  
  METHODS
  The rats were randomized into five groups: sham group, I/R group, HT+I/R group, HT+LY294002+I/R group, and LY+I/R group. Myocardial infarct size, markers of oxidative stress, extent of myocardial apoptosis, echocardiographically assessed cardiac function, and expression of Akt and GSK 3β were measured in each group.
  
  
  RESULTS
  Prereperfusion administration of HT was associated with a significantly smaller area of myocardial infarction and remarkably decreased level of myocardial apoptosis and necrosis, as evidenced by a lower apoptotic index, reduced cleaved caspase-3, and the serum activities of lactate dehydrogenase and creatinine kinase MB. Moreover, HT also attenuated the impairment of cardiac systolic function. However, cotreatment with LY294002 and HT completely abolished the above cardioprotective effects of HT. A subsequent mechanistic study revealed that the cardioprotective effects of HT during the process of I/R of the myocardium were dependent on the activation of the Akt/GSK3β pathway.
  
  
  CONCLUSIONS
  Pretreatment with HT may have antiapoptotic and cardioprotective effects against myocardial I/R injury, and these effects seem to be related to the activation of the Akt/GSK3β pathway in the myocardium.
authors.affiliation: Department of Intensive Care Unit, Jiangsu Provincial Hospital of Traditional Chinese Medicine, The Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, 155 Han Zhong Road, Nanjing 210029, China.
authors.forename: Ying-hao
authors.initials: YH
authors.lastname: Pei
authors.affiliation: Department of Intensive Care Unit, Nanjing Integrated Traditional Chinese and Western Medicine Hospital, Nanjing University of Traditional Chinese Medicine, 179 Xiao Lin-Wei, Nanjing 210014, China.
authors.forename: Jiao
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Cardiology, Jinling Hospital, Nanjing University, School of Medicine, Nanjing 210002, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Xie
authors.affiliation: Department of Cardiology, Jinling Hospital, Nanjing University, School of Medicine, Nanjing 210002, China.
authors.forename: Xiao-min
authors.initials: XM
authors.lastname: Cai
authors.affiliation: Department of Intensive Care Unit, Nanjing Integrated Traditional Chinese and Western Medicine Hospital, Nanjing University of Traditional Chinese Medicine, 179 Xiao Lin-Wei, Nanjing 210014, China.
authors.forename: Run-Hua
authors.initials: RH
authors.lastname: Yang
authors.affiliation: Department of Intensive Care Unit, Jiangsu Provincial Hospital of Traditional Chinese Medicine, The Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, 155 Han Zhong Road, Nanjing 210029, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Jinling Hospital, Nanjing University, School of Medicine, Nanjing 210002, China.
authors.forename: Jian-bin
authors.initials: JB
authors.lastname: Gong
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D004195:Disease Models, Animal; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000378:metabolism* / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000627:therapeutic use; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats
chemical_list: C005975:3,4-dihydroxyphenylethanol; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D010626:Phenylethyl Alcohol