Cardiomyocytes FGFBP1 induction by STAT3 drives pathological cardiac remodeling

Area of Science:

• Cardiovascular Biology
• Molecular Medicine
• Pathology

Background:

• Cardiac remodeling is a key process in heart failure development.
• The specific molecular mechanisms driving pathological cardiac remodeling are not fully understood.

Purpose of the Study:

• To identify novel molecular regulators of pathological cardiac remodeling.
• To investigate the role of fibroblast growth factor binding protein 1 (FGFBP1) in cardiac remodeling.

Main Methods:

• Analysis of FGFBP1 expression in human hypertrophic myocardium and mouse models of cardiac stress (angiotensin II and transverse aortic constriction).
• Assessment of cardiac function, hypertrophy, and fibrosis in FGFBP1 knockout mice.
• RNA sequencing to identify gene expression changes in response to FGFBP1 deficiency.
• Investigation of the STAT3 signaling pathway in cardiomyocytes and the effect of STAT3 inhibition.

Main Results:

• FGFBP1 expression is significantly upregulated in cardiac hypertrophy and pressure overload.
• FGFBP1 deficiency protects against cardiac dysfunction, hypertrophy, and fibrosis induced by Ang II and TAC.
• FGFBP1 knockout suppresses pro-fibrotic and extracellular matrix gene expression in stressed hearts.
• Angiotensin II activates STAT3, which drives FGFBP1 transcription and profibrotic signaling.
• STAT3 inhibition mimics the protective effects of FGFBP1 deficiency.

Conclusions:

• FGFBP1 is a novel and significant contributor to pathological cardiac remodeling.
• The STAT3-FGFBP1 signaling axis plays a critical role in mediating cardiac fibrosis and dysfunction.
• Targeting the STAT3-FGFBP1 pathway represents a potential therapeutic strategy for heart failure.