Integrative Transcriptomic-Histological Analysis in Dilated Cardiomyopathy Unveils FGFR1 Inhibition as Anti-Cardiac...

Area of Science:

• Cardiovascular Research
• Molecular Cardiology
• Translational Medicine

Background:

• Cardiac fibrosis is a key driver of dysfunction in dilated cardiomyopathy (DCM).
• Current therapeutic options for mitigating cardiac fibrosis and improving heart failure outcomes in DCM remain limited.
• Understanding the molecular mechanisms underlying cardiac fibrosis is crucial for developing effective treatments.

Purpose of the Study:

• To identify novel molecular targets for treating cardiac fibrosis in DCM.
• To investigate the role of Fibroblast Growth Factor Receptor 1 (FGFR1) in cardiac fibrosis.
• To evaluate the therapeutic potential of FGFR1 inhibition in preclinical models of DCM.

Main Methods:

• Transcriptomic and histological analyses of 58 human DCM patient biopsies.
• In vitro studies using cardiac organoid models.
• In vivo studies using murine models of DCM.
• Pharmacological inhibition of FGFR1 using AZD4547.

Main Results:

• FGFR1 expression levels were found to significantly correlate with the severity of cardiac fibrosis in human DCM samples.
• Inhibition of FGFR1 with AZD4547 demonstrated a significant reduction in cardiac fibrosis.
• Treatment with AZD4547 led to notable improvements in cardiac function in both organoid and murine models of DCM.
• FGFR1 was identified as a critical molecular target in the pathogenesis of cardiac fibrosis.

Conclusions:

• FGFR1 plays a critical role in the development and progression of cardiac fibrosis in DCM.
• FGFR1 inhibition represents a promising therapeutic strategy for reducing cardiac fibrosis.
• Targeting FGFR1 may offer a novel approach to improve cardiac function and outcomes in patients with heart failure due to DCM.