Neuregulin-1β augments adaptive concentric remodeling and systolic function without exacerbating hypertrophy during...

Area of Science:

• Cardiology
• Molecular Biology
• Physiology

Background:

• Neuregulin-1β (NRG1) improves cardiac output in heart failure.
• Concerns exist regarding ErbB activation promoting maladaptive hypertrophy during hemodynamic stress.

Purpose of the Study:

• Investigate NRG1's influence on structural, functional, and molecular remodeling during pressure overload.
• Determine NRG1's effects on cardiac hypertrophy and decompensation.

Main Methods:

• Male and female mice underwent transverse aortic constriction (TAC) or sham surgery.
• Mice received saline or recombinant NRG1 via osmotic minipumps or injection.
• Cardiac function, structure, fibrosis, macrophage infiltration, and gene expression were analyzed.

Main Results:

• In males, NRG1 increased ejection fraction, accentuated concentric remodeling without hypertrophy, and reduced fibrosis and macrophage infiltration.
• NRG1 amplified TAC-induced Myh7/Nppa expression, shifted Glut1/Glut4 to a fetal profile, and modulated Mybpc2 and Popdc2 expression.
• NRG1 increased Gja1 expression and connexin 43 localization, enhancing electrical coupling. Female mice showed improved function but not reduced fibrosis.

Conclusions:

• NRG1 promotes adaptive remodeling and enhances cardiac performance under pressure overload without exacerbating hypertrophy.
• NRG1-regulated genes are linked to cardiac contraction and conduction, highlighting potential therapeutic mechanisms.
• NRG1 warrants further exploration as a therapeutic strategy for cardiac disease.