Calcineurin in human heart hypertrophy

Area of Science:

• Cardiovascular Biology
• Molecular Cardiology
• Biochemistry

Background:

• Calcineurin pathway signaling is sufficient for cardiac hypertrophy in animal models.
• Elevated calcineurin activity is observed in human heart failure.
• Limited data exist on calcineurin activity in non-failing hypertrophic hearts.

Purpose of the Study:

• To investigate calcineurin activity and protein expression in hypertrophic obstructive cardiomyopathy (HOCM) and aortic stenosis (AS).
• To determine the role of calcineurin in non-failing human cardiac hypertrophy.

Main Methods:

• Assessed calcineurin activity and protein expression in myocardial tissue from HOCM and AS patients.
• Utilized reverse-transcription polymerase chain reaction to detect splice variants.
• Analyzed nuclear factor of activated T cells 2 (NF-AT2) migration via SDS-PAGE.

Main Results:

• Reduced abundance of the calcineurin A C-terminus, suggesting proteolysis, was observed.
• Significantly elevated calcineurin enzymatic activity in HOCM and AS compared to normal hearts.
• Increased calcineurin phosphatase activity led to enhanced NF-AT2 dephosphorylation.

Conclusions:

• Cardiac hypertrophy in HOCM and AS without heart failure shows increased calcineurin activity.
• Partial proteolysis of the calcineurin A C-terminus may contribute to increased activity.
• Calcineurin activation is implicated in the pathogenesis of human cardiac hypertrophy, regardless of the initial trigger.