Single-Stranded DNA-Binding Protein 1 Abrogates Cardiac Fibroblast Proliferation and Collagen Expression Induced by...

Area of Science:

• Cardiology
• Molecular Biology
• Biochemistry

Background:

• The renin-angiotensin system (RAS) component Angiotensin II (Ang II) is a key driver of cardiac fibrosis and heart failure.
• Single-stranded DNA-binding protein 1 (SSBP1) influences mitochondrial function and extracellular matrix remodeling, suggesting a role in fibrotic processes.

Purpose of the Study:

• To investigate the role of SSBP1 in Ang II-induced cardiac fibrosis.
• To elucidate the molecular mechanisms linking SSBP1, p53, and cardiac fibroblast activation.

Main Methods:

• Ang II and valsartan were administered to C57BL/6J mice.
• Echocardiography assessed heart function; picrosirus red staining evaluated cardiac fibrosis.
• Gene expression (COL1A1, COL3A1, SSBP1, p53, Nox1, Nox4) was analyzed via qRT-PCR and immunoblots; SSBP1 and p53 levels were manipulated experimentally.

Main Results:

• Ang II increased heart weight, blood pressure, and cardiac fibrosis, effects reversed by valsartan.
• Ang II induced mitochondrial dysfunction, oxidative stress, and decreased SSBP1 expression.
• SSBP1 knockdown enhanced fibroblast proliferation and collagen expression, while SSBP1 or p53 overexpression counteracted these effects.

Conclusions:

• Ang II down-regulates SSBP1 expression, contributing to cardiac fibroblast proliferation and collagen deposition.
• SSBP1's role in cardiac fibrosis is partly mediated through the p53 protein pathway.
• Targeting SSBP1 or p53 may offer therapeutic strategies for Ang II-induced cardiac fibrosis.