NF-kappaB activation is required for adaptive cardiac hypertrophy

Area of Science:

• Cardiovascular Biology
• Molecular Cardiology
• Cardiac Remodeling

Background:

• Nuclear factor-kappa B (NF-kappaB) plays a role in cardiac hypertrophy.
• Previous studies showed NF-kappaB inhibition attenuates angiotensin II (AngII)-induced left ventricular (LV) hypertrophy.
• The role of NF-kappaB in LV remodeling under chronic stress is not fully understood.

Purpose of the Study:

• To investigate the effect of NF-kappaB inhibition on LV remodeling in response to chronic pressure overload and AngII stimulation.
• To determine if NF-kappaB inhibition can block adverse cardiac remodeling.

Main Methods:

• Cardiac-specific NF-kappaB inhibition using a transgenic mouse model (IkappaBalphaDeltaN under alphaMHC promoter).
• Induction of LV hypertrophy and remodeling via trans-aortic constriction (TAC) and AngII infusion.
• Assessment of LV hypertrophy, fractional shortening (FS), and cardiac fibrosis.

Main Results:

• NF-kappaB inhibition blocked LV hypertrophy in male mice after 4 weeks of low-gradient TAC, but not in females.
• LV remodeling, indicated by decreased FS, was not attenuated by NF-kappaB inhibition after 8 weeks of TAC or high-gradient TAC.
• NF-kappaB inhibition accelerated LV remodeling and increased cardiac fibrosis in an AngII-dependent heart failure model.

Conclusions:

• NF-kappaB inhibition attenuates cardiac hypertrophy in a gender-specific manner.
• NF-kappaB is not required for preventing adverse LV remodeling during chronic pressure overload.
• NF-kappaB appears essential for adaptive cardiac hypertrophy but not maladaptive remodeling.