Effects of the calcineurin dependent signaling pathway inhibition by cyclosporin A on early and late cardiac remodeling following myocardial infarction.
BACKGROUND
The calcineurin-mediated signaling pathway has been implicated as one of the crucial pathways in cardiac hypertrophy. However, the role of calcineurin pathway on cardiac remodeling after myocardial infarction (MI) has not been well defined.


METHODS
Infarcted rats (n = 45) were randomized into calcineurin inhibitor, cyclosporin A (CsA) or vehicle groups, 3 days after MI and treated for 2 weeks (early post-MI cardiac remodeling stage), or randomized 17 days after MI and treated for 2 weeks (late remodeling stage).


RESULTS
Calcineurin pathway inhibition during the early cardiac remodeling stage attenuated the myocardial hypertrophy after MI (P < 0.05). However, left ventricular dimensions were further increased and fractional shortening deteriorated with calcineurin inhibition during this stage (P < 0.05, each). During late remodeling stage, CsA treatment did not affect myocardial hypertrophy and cardiac dilation following MI.


CONCLUSIONS
Our results strongly support the hypothesis that calcineurin pathway mediates compensatory myocardial hypertrophy during the early remodeling stage after MI. However, the calcineurin pathway does not seem to affect the late remodeling after MI.
Youn
Tae-jin
TJ
Department of Internal Medicine, College of Medicine, Chungbuk National University, # 62 Gaeshin-dong, Hungduk-gu, Cheongju 361-711, South Korea.
Piao
Hainan
H
Kwon
Jin-sook
JS
Choi
So-young
SY
Kim
Hyung-sam
HS
Park
Dae-gyun
DG
Kim
Dong-woon
DW
Kim
Young-gyu
YG
Cho
Myeong-chan
MC
D000818:Animals; D019703:Calcineurin / Q000494:pharmacology; D065095:Calcineurin Inhibitors; D016572:Cyclosporine / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004452:Echocardiography; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006334:Heart Function Tests; D006439:Hemodynamics / Q000502:physiology; D017379:Hypertrophy, Left Ventricular / Q000517:prevention & control; D008297:Male; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000188:drug therapy*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function; D012016:Reference Values; D015398:Signal Transduction; D013997:Time Factors; D016896:Treatment Outcome; D020257:Ventricular Remodeling
D065095:Calcineurin Inhibitors; D004791:Enzyme Inhibitors; D016572:Cyclosporine; D019703:Calcineurin