title: Alcohol consumption mitigates apoptosis and mammalian target of rapamycin signaling in myocardium.
abstract: BACKGROUND
  Epidemiologic studies have shown that individuals who consume low to moderate alcohol have a lower risk of cardiovascular disease developing compared with abstainers. Although experimental studies confirmed this observation, the effect of alcohol on ischemic myocardium is still unclear. We developed a clinically relevant animal model of chronic myocardial ischemia to investigate the effects of moderate alcohol consumption on the myocardium.
  
  
  METHODS
  Fourteen Yorkshire swine underwent placement of an ameroid constrictor to induce chronic myocardial ischemia. Postoperatively, one group was supplemented with 90 mL 50% EtOH daily (n = 7) and one group was supplemented with 80 g sucrose daily to normalize caloric intake between groups (n = 7). After 7 weeks, all animals underwent sternotomy, and harvest of the chronically ischemic myocardium and nonischemic myocardium. Tissues were analyzed for protein expression and stained for apoptosis quantification.
  
  
  RESULTS
  In the ischemic myocardium, alcohol down-regulated the following proapoptotic proteins: tumor necrosis factor-α, forkhead box protein 03, BCL2-associated death promoter, and cysteine aspartic acid-specific protease 9; up-regulated the following prosurvival proteins: 5'adenosine monophosphate-activated protein kinase, phosphorylated 5'adenosine monophosphate-activated protein kinase, and phosphorylated forkhead box protein 03; and down-regulated mammalian target of rapamycin (MTOR) signaling by down-regulating MTOR, phosphorylated MTOR, and up-regulating Deptor. In the nonischemic myocardium, alcohol up-regulated prosurvival proteins: protein kinase B, phosphorylated protein kinase B, phosphorylated B-cell CLL/lymphoma 2, 5'adenosine monophosphate-activated protein kinase, phosphorylated BCL2-associated death promoter, phosphorylated forkhead box protein 03, and down-regulated MTOR signaling by down-regulating phosphorylated MTOR and up-regulating Deptor. Alcohol also decreased cell death as measured by terminal deoxynucleotidyl transferase mediated dUTP nick-end labeling staining in the ischemic and nonischemic myocardium.
  
  
  CONCLUSIONS
  Alcohol consumption down-regulates apoptosis and promotes cell survival in the ischemic and nonischemic myocardium. Alcohol also modulates MTOR signaling, which regulates senescence and apoptosis. Perhaps MTOR and apoptosis regulation is another mechanism by which moderate EtOH consumption is cardioprotective.
authors.affiliation: Division of Cardiothoracic Surgery, Cardiovascular Research Center, Warren Alpert School of Medicine, Brown University, Providence, RI.
authors.forename: Nassrene Y
authors.initials: NY
authors.lastname: Elmadhun
authors.affiliation: Division of Cardiothoracic Surgery, Cardiovascular Research Center, Warren Alpert School of Medicine, Brown University, Providence, RI.
authors.forename: Ashraf A
authors.initials: AA
authors.lastname: Sabe
authors.affiliation: Division of Cardiothoracic Surgery, Cardiovascular Research Center, Warren Alpert School of Medicine, Brown University, Providence, RI.
authors.forename: Antonio D
authors.initials: AD
authors.lastname: Lassaletta
authors.affiliation: Division of Cardiothoracic Surgery, Cardiovascular Research Center, Warren Alpert School of Medicine, Brown University, Providence, RI. Electronic address: fsellke@lifespan.org.
authors.forename: Frank W
authors.initials: FW
authors.lastname: Sellke
mesh_terms: D000428:Alcohol Drinking; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D000431:Ethanol / Q000494:pharmacology*; D008297:Male; D017202:Myocardial Ischemia / Q000517:prevention & control; D009206:Myocardium; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects*; D013552:Swine; D013556:Swine, Miniature; D058570:TOR Serine-Threonine Kinases / Q000187:drug effects* / Q000502:physiology*
chemical_list: D000431:Ethanol; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases