Cardioprotection by ischemic postconditioning is abolished in depressed rats: role of Akt and signal transducer and activator of transcription-3.
Ischemic postconditioning (IPC) represents one of the most effective cardioprotective strategies against myocardial ischemia/reperfusion. Depression is commonly present in patients with coronary heart disease. However, whether depression interferes with the cardioprotection of IPC during myocardial ischemia/reperfusion and their underlying mechanisms remain largely unknown. Isolated hearts from chronic mild stress induced-depressed rats and non-depressed rats were subjected to 30 min of regional ischemia followed by 120 min of reperfusion in the presence or absence of IPC (consisting of 6 cycles of 10 s of reperfusion and 10 s of ischemia immediately after the sustained ischemia). Myocardial infarct size, creatine kinase (CK) and cardiac troponin T (cTnT) release, cardiac function and phosphorylated AKT and signal transducer and activator of transcription-3 (STAT-3) were measured. IPC significantly prevented the hearts from myocardial ischemia/reperfusion injury by decreasing infarct size, and CK and cTnT release in coronary effluent, and improving cardiac functional recovery in non-depressed rats. However, these cardioprotective effects of IPC were not observed in depressed rats. In addition, IPC had no effects on the phosphorylation of AKT and STAT-3 at reperfusion in depressed hearts, although it markedly increased the phosphorylation of AKT and STAT-3 at reperfusion in non-depressed hearts. In conclusion, these data indicate that cardioprotection by IPC is abolished during myocardial ischemia/reperfusion in depressed rats, and the underlying mechanisms are probably related to the impaired activation of AKT and STAT-3 at reperfusion.
Zhuo
Chuanjun
C
Department of Psychiatry, Anning Hospital of Tianjin City, No. 20 Yongping Lane, Dongli District, Tianjin, 300300, China.
Wang
Ying
Y
Wang
Xiaohui
X
Wang
Yufen
Y
Chen
Yuhui
Y
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D015153:Blotting, Western; D003402:Creatine Kinase / Q000378:metabolism; D003863:Depression / Q000503:physiopathology*; D057775:Ischemic Postconditioning; D008055:Lipids / Q000097:blood; D008297:Male; D009203:Myocardial Infarction / Q000503:physiopathology*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D020107:Troponin T / Q000378:metabolism*
D001786:Blood Glucose; D008055:Lipids; D050796:STAT3 Transcription Factor; D020107:Troponin T; D051057:Proto-Oncogene Proteins c-akt; D003402:Creatine Kinase