Septin4 Regulates Cardiac Fibrosis After Pressure Overload

Area of Science:

• Cardiovascular Biology
• Molecular Cardiology
• Fibrosis Research

Background:

• Cardiac remodeling post-injury can lead to heart failure.
• Septin4 (Sept4) is involved in regeneration and apoptosis in other organs.
• The role of Sept4 in cardiac stress response is currently unknown.

Purpose of the Study:

• To investigate the role of Sept4 in cardiac remodeling and response to injury.
• To determine if Sept4 deficiency confers protection against cardiac stress.

Main Methods:

• Utilized wild-type and Sept4 knockout mice subjected to transverse aortic constriction.
• Generated fibroblast-specific Sept4 conditional knockout mice.
• Assessed cardiac function, apoptosis, fibrosis, and extracellular matrix deposition at various time points.

Main Results:

• Sept4 knockout mice maintained normal cardiac function and reduced cardiomyocyte apoptosis after injury.
• Knockout hearts showed decreased fibrosis and extracellular matrix deposition.
• Sept4 deficiency altered calcineurin-dependent signaling in fibroblasts, reducing myofibroblast activation.

Conclusions:

• Sept4 is a critical regulator of cardiac extracellular matrix remodeling.
• Sept4 controls fibroblast to myofibroblast conversion via calcineurin-dependent pathways.
• Targeting Sept4 may offer a therapeutic strategy for heart failure.