Disruption of coordinated cardiac hypertrophy and angiogenesis contributes to the transition to heart failure

Area of Science:

• Cardiovascular Biology
• Molecular Cardiology
• Cardiac Physiology

Background:

• Sustained cardiac overload often leads to heart failure via poorly understood mechanisms.
• Cardiac hypertrophy initially preserves contractility but can progress to dilated cardiomyopathy.

Purpose of the Study:

• To investigate the role of angiogenesis in the transition from adaptive cardiac hypertrophy to heart failure.
• To elucidate the mechanisms linking Akt1 activation, cardiac growth, and angiogenesis.

Main Methods:

• A conditional transgenic mouse model with inducible activated Akt1 in the heart was utilized.
• Analysis of cardiac structure, function, coronary angiogenesis, and molecular signaling (VEGF, angiopoietin-2, mTOR).
• Inhibition of angiogenesis using a decoy VEGF receptor.

Main Results:

• Activated Akt1 induced sequential adaptive hypertrophy and dilated cardiomyopathy.
• Coronary angiogenesis was enhanced during adaptive growth but reduced during pathological remodeling.
• Angiogenesis inhibition impaired cardiac growth, reduced capillary density, and caused contractile dysfunction.

Conclusions:

• Heart size and function are dependent on coordinated angiogenesis.
• Disruption of the balance between cardiac growth and angiogenesis contributes to the progression of heart failure.
• Targeting angiogenesis may offer therapeutic strategies for heart failure.