Role of Calcineurin-Dependent Signaling Pathway on the Left Ventricular Hypertrophy Induced by Pressure Overload.
10.4070/kcj.2001.31.11.1159
- Author:
Hainan PIAO
1
;
Jin Sook KWON
;
Hye Young LEE
;
Tae Jin YOUN
;
Dong Woon KIM
;
Seung Taik KIM
;
Bo Ra SON
;
Young Gyu KIM
;
Kwang Ju LEE
;
Byung Kwan LIM
;
Eun Seok JEON
;
Myeong Chan CHO
Author Information
1. Department of Internal Medicine, College of Medicine, Chungbuk National University, Cheongju, Korea. mccho@med.chungbuk.ac.kr
- Publication Type:Original Article
- Keywords:
Calcineurin;
Hypertrophy;
Myocardium;
Cyclosporine;
Tacrolimus
- MeSH:
Animals;
Calcineurin;
Cardiomegaly;
Cyclosporine;
Fibrosis;
Hypertrophy;
Hypertrophy, Left Ventricular*;
Mice;
Mice, Inbred ICR;
Myocardium;
Tacrolimus
- From:Korean Circulation Journal
2001;31(11):1159-1170
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
BACKGROUND AND OBJECTIVES: Calcineurin-dependent transcriptional pathway has recently been implicated in cardiac hypertrophy. Whether calcineurin inhibition can prevent the development of pressure-overload left ventricular hypertrophy (LVH) is still controversial. To elucidate this issue, the effects of calcineurin inhibitors on the prevention of pressure-overload LVH were examined in mice. MATERIALS AND METHODS: Pressure overload was induced by transverse aortic contriction (TAC) in 57 ICR mice. Three different doses of CsA (TAC/CsA group, n=21) and FK506 (TAC/FK group, n=20) were administered subcutaneously from -2 to 14 days after surgery and 16 mice were treated with vehicle (TAC group). Another 60 mice were sham-operated and treated with CsA (CsA group, n=19), FK506 (FK group, n=18) or vehicle (Control group, n=23). RESULTS: Two weeks after TAC, the LV weight-to-body weight (LVW/BW) ratio was not significantly different among the Control, CsA and FK groups although it was greater in the TAC group (4.55+/-0.69 mg/g) than in the Control(2.78+/-0.70 mg/g) and other sham-operated groups (p<0.00005). Low-dose CsA (5 mg/kg/day) or FK506 (0.6 mg/kg/day) injection following TAC did not decrease the LVW/BW ratio. However, intermediate-dose and high-dose CsA (25 and 50 mg/kg/day) or FK506 (2 and 6 mg/kg/day) treatment prevented pressure-overload induced LVH and the degree of LVH inhibition was dose-dependent. Interstitial and/or perivascular fibrosis was remarkably decreased by the administration of intermediate and high doses of calcineurin inhibitors for 2 weeks following TAC. CONCLUSION: Taken together, calcineurin inhibitors, CsA and FK506, attenuated pressure-overload LVH response in a dose-dependent fashion. This data indicates that a calcineurin-dependent signaling pathway is crucial in the development of pressure-overload LVH.
