Protective effect of C5 shRNA on myocardial ischemia-reperfusion injury in rats.
Myocardial ischemia and reperfusion (MI/R) injury is associated with activation of the complement system. Complement activation generates a series of bioactive substances, including early (C3a, C3b) and terminal (C5a, C5b-9) components. The terminal complement components are key mediators of MI/R injury. This study investigated whether C5 shRNA preconditioning has protective effects following MI/R injury and its potential mechanism. Rats were injected with C5 shRNA 2 days before induction of ischemia. The effects of C5 shRNA were evaluated by the assessment of heart function, infarct size, histopathology, inflammatory cytokine levels, and the plasma level of troponin T. Akt phosphorylation was assessed by immunoblotting. C5 shRNA efficiently inhibited C5 expression both in vitro and in vivo, and attenuated MI/R injury. C5 shRNA preconditioning significantly decreased the level of troponin T and the production of pro-inflammatory cytokine. The infarct size was decreased by 40% in C5 shRNA treated rats. Akt phosphorylation increased after C5 shRNA preconditioning. These results suggest that C5 shRNA preconditioning in rats has protective effects following MI/R injury; this may be partly effected by mediating the activation of the PI3K pathway and by phosphorylation of Akt.
Department of Cardiology, First Affiliated Hospital, Sun Yat-Sen University, No. 58 Zhongshan Road II, Guangzhou, GD510080, China.
Kai
K
Tang
Yunjiu
Y
Cheng
Suhua
S
Wu
Lijuan
L
Liu
Lingli
L
Cheng
D000818:Animals; D003182:Complement C5 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D020868:Gene Silencing; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D009203:Myocardial Infarction / Q000235:genetics / Q000517:prevention & control; D017202:Myocardial Ischemia / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000235:genetics / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D058539:Phosphatidylinositol 3-Kinase / Q000737:chemistry / Q000378:metabolism; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034741:RNA, Small Interfering / Q000627:therapeutic use*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D015854:Up-Regulation; D018487:Ventricular Dysfunction, Left / Q000235:genetics / Q000517:prevention & control
D003182:Complement C5; D034741:RNA, Small Interfering; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt