Cardiomyocyte SORBS2 expression increases in heart failure and regulates integrin interactions and extracellular...

Area of Science:

• Cardiology
• Molecular Biology
• Genomics

Background:

• Cardiomyocyte stress is a hallmark of heart failure.
• Understanding the genetic underpinnings of cardiac remodeling is crucial for developing targeted therapies.

Purpose of the Study:

• To identify genes associated with stressed cardiomyocytes using integrated transcriptomic data.
• To investigate the role of conserved genes in cardiac pathology.

Main Methods:

• Combined single-cell transcriptomic datasets from human and mouse failing hearts.
• Bioinformatic analysis to identify conserved genes.
• Utilized mouse models and human cardiac tissue for validation.
• Affinity purification mass spectrometry to identify protein interactions.

Main Results:

• Identified SORBS2 as a conserved NPPA-correlated gene.
• SORBS2 expression increases during pathological cardiac remodeling and correlates with disease severity.
• GATA4 regulates SORBS2 expression.
• SORBS2 interacts with integrin-cytoskeleton complexes.
• Loss of Sorbs2 in mice exacerbates fibrosis by altering integrin interactions and extracellular matrix components.

Conclusions:

• SORBS2 is upregulated in heart failure in a GATA4-dependent manner.
• SORBS2 is a crucial regulator of integrin interactions and cardiac fibrosis.
• Targeting SORBS2 may offer therapeutic potential for heart failure.