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Calcineurin expression, activation, and function in cardiac pressure-overload hypertrophy
H W Lim1, L J De Windt, L Steinberg
1Department of Pediatrics, Children's Hospital Medical Center, University of Cincinnati, Ohio, USA.
Circulation
|May 24, 2000
Summary
Calcineurin activity increases with cardiac load, contributing to heart hypertrophy. Inhibiting calcineurin with cyclosporine A (CsA) attenuated and partially reversed this hypertrophy in rats.
Area of Science:
- Cardiovascular Biology
- Molecular Cardiology
- Physiology
Background:
- Vascular hypertension increases cardiac load, leading to left ventricular hypertrophy and heart disease.
- Molecular pathways regulating cardiac hypertrophy are not fully understood.
- Calcineurin, a calcium-sensitive phosphatase, is a potential regulator of cardiac hypertrophy.
Purpose of the Study:
- To investigate the role of calcineurin in pressure-overload-induced cardiac hypertrophy.
- To determine if calcineurin activity and expression increase with cardiac load.
- To assess the effect of calcineurin inhibition on cardiac hypertrophy.
Main Methods:
- Induced pressure-overload hypertrophy in rats via abdominal aortic banding.
- Measured calcineurin enzymatic activity and protein content in heart tissue.
- Utilized Western blot analysis to assess calcineurin and calmodulin association.
- Administered cyclosporine A (CsA), a calcineurin inhibitor, to rats.
Main Results:
- Calcineurin enzymatic activity and protein content increased significantly in response to pressure-overload hypertrophy.
- Increased calcineurin protein content was associated with increased calmodulin binding.
- CsA administration prevented and partially reversed cardiac hypertrophy in a dose-dependent manner.
- CsA treatment attenuated histological and molecular markers of hypertrophy.
Conclusions:
- Calcineurin is a key upstream regulator of load-induced cardiac hypertrophy.
- Inhibiting calcineurin with CsA offers a potential therapeutic strategy for managing cardiac hypertrophy.
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