Tranilast stabilizes the accumulation and degranulation of resident mast cells while reducing cardiomyocyte apoptosis in a swine model of coronary microembolisation.
1. Coronary microembolisation (CME) is associated with progressive myocardial dysfunction, and mast cells (MC) might have an important role in myocardial apoptosis after CME. We investigated whether the MC stabilizer tranilast suppresses the accumulation and degranulation of MC while reducing cardiomyocyte apoptosis after CME. 2. We induced CME in miniswine by selective infusion of 15 x 10(4) microspheres (diameter 45 microm) into the left anterior descending artery. Some CME-induced miniswine were treated with the MC stabilizer tranilast (50 mg/kg, p.o., b.d.) beginning 2 weeks before CME, and thereafter throughout the experimental period; others received tranilast without CME; and sham-operated animals without CME served as controls. After 30 days, we assessed cardiomyocyte apoptosis by TUNEL assay and by the total number of MC and the number of degranulating MC using histology and transmission electron microscopy. The wall motion score index and left ventricular ejection fraction were studied by dobutamine stress echocardiography. 3. Coronary microembolisation was associated with increases in the total number of MC, the number of degranulating MC, and myocyte apoptosis. The number of total MC and degranulating MC and apoptotic cardiomyocytes over the anterior embolized myocardium after CME were significantly higher than those over the posterior control myocardium and anterior segments per animal without CME (P < 0.01). Tranilast administration to CME miniswine suppressed cardiomyocyte apoptosis while maintaining regional and global function, which was associated with reductions in the accumulation and degranulation of MC. 4. These findings suggest that tranilast suppresses the accumulation and degranulation of MC while reducing cardiomyocyte apoptosis after CME.
Division of Cardiology, Number 6 People's Hospital, Jiaotong University, Shanghai 200233, China. yeakcardio@yahoo.com.cn
Qing-Yong
QY
Zhang
Jing-Bo
JB
Li
Zhi-Hua
ZH
Wang
Xiao-Bo
XB
Li
Lian-Hua
LH
Yin
Meng
M
Wei
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015550:Cell Degranulation / Q000187:drug effects*; D003331:Coronary Vessels / Q000187:drug effects* / Q000648:ultrastructure; D004195:Disease Models, Animal; D025401:Echocardiography, Stress; D004617:Embolism / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D020287:In Situ Nick-End Labeling; D008297:Male; D008407:Mast Cells / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D046529:Microscopy, Electron, Transmission; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000648:ultrastructure; D013552:Swine; D013556:Swine, Miniature; D062367:ortho-Aminobenzoates / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*
D062367:ortho-Aminobenzoates; C012293:tranilast