Carbonic anhydrase II promotes cardiomyocyte hypertrophy

Area of Science:

• Cardiovascular Physiology
• Molecular Cardiology
• Biochemistry

Background:

• Pathological cardiac hypertrophy is a maladaptive myocardial remodeling process that can lead to heart failure.
• The sodium-proton exchanger (NHE1) and chloride-bicarbonate exchanger (AE3) are implicated in cardiac hypertrophy.
• Carbonic anhydrase II (CAII) provides substrates for NHE1 and AE3 and interacts with them, enhancing their activity.

Purpose of the Study:

• To investigate the specific role of cytosolic carbonic anhydrase II (CAII) in promoting pathological cardiac hypertrophy.
• To determine if CAII's catalytic activity or its interaction with ion transporters is crucial for hypertrophy.

Main Methods:

• Over-expression of wild-type and catalytically inactive CAII (CAII-V143Y) in neonatal rat ventricular myocytes (NRVMs) using adenoviral constructs.
• Assessment of cardiomyocyte hypertrophy (CH) response to hypertrophic stimuli.
• Analysis of cardiac phenotype and function in CAII-deficient (Car2) mice.

Main Results:

• Over-expression of wild-type CAII did not affect CH.
• Over-expression of catalytically inactive CAII-V143Y suppressed the hypertrophic response in NRVMs, indicating a dominant-negative effect.
• CAII-deficient mice hearts showed physiological hypertrophy without impaired cardiac function, and their cardiomyocytes were unresponsive to hypertrophic stimuli.

Conclusions:

• Cytosolic CAII plays a critical role in promoting pathological cardiac hypertrophy.
• CAII's catalytic activity, rather than its mere presence, is essential for mediating hypertrophy.
• Targeting CAII activity may offer a therapeutic strategy for preventing pathological cardiac remodeling.