title: Differences in myocardial PTEN expression and Akt signalling in type 2 diabetic and nondiabetic patients undergoing coronary bypass surgery.
abstract: OBJECTIVE
  Patients with diabetes experience increased cardiovascular complications after cardiac surgery. Hyperglycaemia predicts increased mortality after myocardial infarction and may influence cardiovascular risk in humans. Impaired prosurvival phosphatase and tensin homologue on chromosome 10 (PTEN)-Akt signalling could be an important feature of the diabetic heart rendering it resistant to preconditioning. This study was designed to evaluate for differences and relationships of myocardial PTEN-Akt-related signalling and baseline glycaemic control marker in type 2 diabetic and nondiabetic patients undergoing coronary artery bypass surgery.
  
  
  METHODS
  Right atrial biopsies and coronary sinus blood were obtained from 18 type 2 diabetic and 18 nondiabetic patients intraoperatively. Expression and phosphorylation of Akt, endothelial nitric oxide synthase (eNOS), Bcl-2 and PTEN were evaluated by Western blot. Plasma 15-F(2t) -isoprostane concentrations were evaluated by liquid chromatography-mass spectrometry.
  
  
  RESULTS
  PTEN expression and 15-F(2t) -isoprostane concentrations were significantly higher in diabetic patients. Increased fasting blood glucose levels correlated with increased coronary sinus plasma 15-F(2t) -isoprostane concentrations. Increased cardiac 15-F(2t) -isoprostane generation was highly correlated with myocardial PTEN expression. Bcl-2 expression and eNOS phosphorylation were significantly lower in diabetic compared with nondiabetic patients. Akt phosphorylation tended to be lower in diabetic patients; however, this tendency failed to reach statistical significance.
  
  
  CONCLUSIONS
  The current results suggest that prosurvival PTEN-Akt signalling is impaired in the diseased diabetic myocardium. Hyperglycaemia and increased oxidative stress may contribute to this phenomenon. These findings strengthen the understanding of the underlying biologic mechanisms of cardiac injury in diabetic patients, which could facilitate development of new treatments to prevent cardiovascular complications in this high-risk population.
authors.affiliation: Department of Anesthesiology, Pharmacology and Therapeutics, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Baohua
authors.initials: B
authors.lastname: Wang
authors.forename: Koen
authors.initials: K
authors.lastname: Raedschelders
authors.forename: Jayant
authors.initials: J
authors.lastname: Shravah
authors.forename: Yu
authors.initials: Y
authors.lastname: Hui
authors.forename: Hajieh G
authors.initials: HG
authors.lastname: Safaei
authors.forename: David D Y
authors.initials: DD
authors.lastname: Chen
authors.forename: Richard C
authors.initials: RC
authors.lastname: Cook
authors.forename: Guy
authors.initials: G
authors.lastname: Fradet
authors.forename: Calvin L
authors.initials: CL
authors.lastname: Au
authors.forename: David M
authors.initials: DM
authors.lastname: Ansley
mesh_terms: D000368:Aged; D015153:Blotting, Western; D002318:Cardiovascular Diseases / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D002853:Chromatography, Liquid; D001026:Coronary Artery Bypass; D054326:Coronary Sinus / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000378:metabolism*; D015237:Dinoprost / Q000031:analogs & derivatives / Q000097:blood / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; C075750:8-epi-prostaglandin F2alpha; D015237:Dinoprost; D052250:Nitric Oxide Synthase Type III; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human