title: The effects of escitalopram on myocardial apoptosis and the expression of Bax and Bcl-2 during myocardial ischemia/reperfusion in a model of rats with depression.
abstract: BACKGROUND
  Major depressive disorder (MDD) is an independent risk factor for coronary heart disease (CHD), and influences the occurrence and prognosis of cardiovascular events. Although there is evidence that antidepressants may be cardioprotective after acute myocardial infarction (AMI) comorbid with MDD, the operative pathophysiological mechanisms remain unclear. Our aim was therefore to explore the molecular mechanisms of escitalopram on myocardial apoptosis and the expression of Bax and Bcl-2 in a rat model of depression during myocardial ischemia/reperfusion (I/R).
  
  
  METHODS
  Rats were divided randomly into 3 groups (n = 8): D group (depression), DI/R group (depression with myocardial I/R) and escitalopram + DI/R group. The rats in all three groups underwent the same chronic mild stress and separation for 21 days, at the same time, in the escitalopram + DI/R group, rats were administered escitalopram by gavage (10 mg/kg/day). Ligation of the rat's left anterior descending branch was done in the myocardial I/R model. Following which behavioral tests were done. The size of the myocardial infarction was detected using 1.5% TTC dye. The Tunel method was used to detect apoptotic myocardial cells, and both the Rt-PCR method and immunohistochemical techniques were used to detect the expression of Bcl-2 and Bax.
  
  
  RESULTS
  Compared with the D and DI/R groups, rats in Escitalopram + DI/R group showed significantly increased movements and sucrose consumption (P < .01). Compared with the DI/R group, the myocardial infarct size in the escitalopram + DI/R group was significantly decreased (P < .01). Compared with the D group, there were significantly increased apoptotic myocardial cells in the DI/R and escitalopram + DI/R groups (P < .01); however compared with the DI/R group, apoptotic myocardial cell numbers in the escitalopram + DI/R group were significantly decreased (P < .01). Compared with the DI/R group, there was a down-regulated Bax:Bcl-2 ratio in the escitalopram + DI/R group (P < .01).
  
  
  CONCLUSIONS
  These results suggest that in patients with AMI comorbid with MDD, there is an increase in pro-apoptotic pathways that is reversed by escitalopram. This suggests that clinically escitalopram may have a direct cardioprotective after acute myocardial infarction.
authors.affiliation: Department of Psychiatry, Hospital Affiliated to Guiyang Medical University, Guiyang, Guizhou, 550004, China. yimingw66@yahoo.com.
authors.forename: Yiming
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Cardiology, The General Hospital of Jinan Military Region, Jinan, 250031, China. zhanghongming1971@163.com.
authors.forename: Hongming
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Psychiatry, Hospital Affiliated to Guiyang Medical University, Guiyang, Guizhou, 550004, China. 310087151@qq.com.
authors.forename: Fangxian
authors.initials: F
authors.lastname: Chai
authors.affiliation: Department of Cardiology, Hospital Affiliated to Medical University, 28 Guiyi Street, Guiyang City, Guizhou, 550004, China. lxdwangyiming@aliyun.com.
authors.forename: Xingde
authors.initials: X
authors.lastname: Liu
authors.affiliation: IMPACT Strategic Research Centre, School of Medicine, Deakin University, Geelong, 3220, Australia. mikebe@barwonhealth.org.au.|School of Public Health and Preventive Medicine, Monash University, Melbourne, 3004, Australia. mikebe@barwonhealth.org.au.|Department of Psychiatry, The University of Melbourne, Parkville, VIC, 3050, Australia. mikebe@barwonhealth.org.au.|Orygen Youth Health Research Centre, The University of Melbourne, Parkville, VIC, 3050, Australia. mikebe@barwonhealth.org.au.|Florey Institute of Neuroscience and Mental Health, University of Melbourne, Level 3, Alan Gilbert Building, Parkville, VIC, 3010, Australia. mikebe@barwonhealth.org.au.
authors.forename: Michael
authors.initials: M
authors.lastname: Berk
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D015283:Citalopram / Q000494:pharmacology / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000188:drug therapy / Q000378:metabolism* / Q000523:psychology; D004195:Disease Models, Animal; D006801:Humans; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism* / Q000523:psychology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016896:Treatment Outcome; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis*
chemical_list: C494828:Bax protein, rat; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D015283:Citalopram