Reduced endoglin activity limits cardiac fibrosis and improves survival in heart failure

Area of Science:

• Cardiovascular Biology
• Molecular Medicine
• Fibrosis Research

Background:

• Heart failure is a leading cause of death globally.
• Transforming growth factor-β1 (TGFβ1) drives cardiac fibrosis, worsening heart failure.
• Endoglin, a TGFβ1 signaling coreceptor, is implicated in vascular remodeling.

Purpose of the Study:

• To investigate the role of endoglin in cardiac fibrosis.
• To determine if targeting endoglin can mitigate heart failure progression.

Main Methods:

• Assessed endoglin expression in human heart failure samples.
• Utilized neutralizing antibodies and siRNA to block TGFβ1 signaling in cardiac fibroblasts.
• Employed a mouse model of pressure-overload-induced heart failure.
• Investigated the effects of soluble endoglin in vitro and in vivo.

Main Results:

• Endoglin expression is elevated in human heart failure ventricles.
• Endoglin is essential for TGFβ1 signaling in human cardiac fibroblasts.
• Reduced endoglin attenuated cardiac fibrosis, preserved function, and improved survival in mice.
• Soluble endoglin inhibited TGFβ1 signaling and collagen synthesis in fibroblasts and reduced fibrosis in vivo.

Conclusions:

• Endoglin is a key mediator of TGFβ1 signaling in cardiac fibroblasts.
• Targeting endoglin effectively reduces cardiac fibrosis.
• Endoglin inhibition presents a promising therapeutic avenue for heart failure treatment.