Korean Circ J.
2001 Nov;31(11):1159-1170. 10.4070/kcj.2001.31.11.1159.
Role of Calcineurin-Dependent Signaling Pathway on the Left Ventricular Hypertrophy Induced by Pressure Overload
- Affiliations
-
- 1Department of Internal Medicine, College of Medicine, Chungbuk National University, Cheongju, Korea. mccho@med.chungbuk.ac.kr
- 2Department of Clinical Pathology, College of Medicine, Chungbuk National University, Cheongju, Korea.
- 3Department of Neurosurgery, College of Medicine, Chungbuk National University, Cheongju, Korea.
- 4Department of Pathology, Chungbuk National University Hospital, Cheongju, Korea.
- 5Department of Internal Medicine, College of Medicine, Soonchunhyang University, Bucheon, Korea.
- 6Chungbuk National University Medical Research Institute, Cheongju, Korea.
- KMID: 1938935
- DOI: http://doi.org/10.4070/kcj.2001.31.11.1159
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.
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