Pathophysiological roles of FGF signaling in the heart

Area of Science:

• Cardiology
• Molecular Biology
• Biochemistry

Background:

• Cardiac remodeling is a key process leading to heart failure, a major cause of death.
• Cardiomyokines, proteins secreted by the heart, are implicated in cardiac remodeling.
• Fibroblast growth factors (FGFs) are a family of secreted proteins with diverse roles, including in cardiac pathophysiology.

Purpose of the Study:

• To elucidate the specific roles and mechanisms of various FGFs in cardiac remodeling.
• To investigate how different FGFs interact with their receptors and co-receptors in the heart.
• To explore the potential of FGFs as therapeutic targets for heart failure.

Main Methods:

• Review and synthesis of existing literature on FGFs in cardiac remodeling.
• Analysis of signaling pathways activated by specific FGFs (e.g., MAPK, calcineurin/NFAT).
• Examination of the roles of FGF receptors (FGFRs) and Klotho co-receptors in mediating FGF effects.

Main Results:

• FGF2 promotes cardiac hypertrophy and fibrosis via FGFR1c and MAPK signaling.
• FGF16 may counteract FGF2 effects by competing for FGFR1c binding.
• FGF21 prevents hypertrophy through FGFR1c/β-Klotho/MAPK signaling, while FGF23 induces hypertrophy via calcineurin/NFAT signaling without α-Klotho.

Conclusions:

• FGFs play critical and distinct roles in cardiac remodeling through diverse mechanisms.
• Understanding these FGF-mediated pathways provides novel insights into heart failure pathogenesis.
• Targeting specific FGFs or their signaling pathways may offer new therapeutic strategies for heart failure.