[Effects of neuregulin on cardiac myocyte apoptosis and PI-3K signal transduction pathway in rapid pacing-induced heart failure in rhesus monkeys].
OBJECTIVE
To explore the protective effect of neuregulin against cardiac myocyte injury in pacing-induced heart failure in rhesus monkeys and its mechanism.


METHODS
Rapid pacing was used to induce heart failure in rhesus monkeys. Aorta intubation was used to perform hemodynamic measurements such as the peak positive rate of of left ventricular pressure (LVdP/dtmax) and left ventricular systolic, end-diastolic blood pressures (LVSP and LVEDP, respectively) 17 days after the pacing. N-terminal pro-brain natriuretic peptide (BNP), as molecular marker of heart failure, was also measured by electrochemical luminescence immunoassay. The apoptosis of cardiac myocyte was observed by Tunel method. Western blot was used to detect the PKB activity and the relative amounts of Bcl-xl protein in the left ventricular free walls.


RESULTS
After the daily intravenous injection of 3microg/kg recombinated neuregulin for 10 days, LVdP/dtmax increased significantly while BNP decreased remarkably. The apoptotic index was obviously lower, and Bcl-xl and activity of PKB were higher.


CONCLUSIONS
Neuregulin protects against rapid pacing-induced apoptosis in heart failure in rhesus monkeys and the mechanism might be attributed to the increase of the activity of PKB and Bcl-xl protein.
Li
Jiang
J
West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
Qiang
Ou
O
Wang
Li
L
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002304:Cardiac Pacing, Artificial / Q000009:adverse effects; D006333:Heart Failure / Q000209:etiology / Q000503:physiopathology*; D020287:In Situ Nick-End Labeling; D008253:Macaca mulatta; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D020880:Neuregulins / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D051020:bcl-X Protein / Q000378:metabolism
D020880:Neuregulins; D051020:bcl-X Protein; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt