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CIB1 is a regulator of pathological cardiac hypertrophy
Joerg Heineke1, Mannix Auger-Messier, Robert N Correll
1Howard Hughes Medical Institute, Department of Pediatrics, University of Cincinnati, Cincinnati, OH, USA. Heineke.Joerg@mh-hannover.de
Nature Medicine
|July 20, 2010
Summary
Calcium and Integrin Binding Protein-1 (CIB1) regulates cardiomyocyte hypertrophy by anchoring calcineurin to the sarcolemma. CIB1 is crucial for pathological cardiac hypertrophy but not physiological responses.
Area of Science:
- Cardiovascular Biology
- Molecular Cardiology
- Cell Signaling
Background:
- Hypertrophic heart disease is a significant health concern in Western nations.
- Identifying novel regulators of cardiomyocyte hypertrophy is critical for therapeutic development.
Purpose of the Study:
- To identify novel regulators of cardiomyocyte hypertrophy.
- To elucidate the role of Calcium and Integrin Binding Protein-1 (CIB1) in cardiac hypertrophy.
Main Methods:
- Yeast two-hybrid screening to identify CIB1-interacting partners.
- Localization studies in mouse and human myocardium.
- Analysis of CIB1 expression and membrane association in physiological and pathological hypertrophy.
- Phenotypic analysis of CIB1-deleted and CIB1-overexpressing mice under pressure overload and exercise stimuli.
Main Results:
- CIB1 interacts with calcineurin B, a subunit of calcineurin.
- CIB1 anchors calcineurin to the sarcolemma, regulating its activation.
- CIB1 levels and membrane association increase in pathological hypertrophy.
- Cib1 deletion attenuates pressure overload-induced cardiac hypertrophy, fibrosis, and dysfunction.
- CIB1 deletion does not affect exercise-induced physiological hypertrophy.
- CIB1 overexpression exacerbates cardiac hypertrophy.
Conclusions:
- CIB1 is a novel regulator of cardiac hypertrophy.
- CIB1 mediates pathological cardiac hypertrophy by controlling calcineurin localization and activation at the sarcolemma.
- CIB1 represents a potential therapeutic target for hypertrophic heart disease.
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