HE4 Predicts Progressive Fibrosis and Cardiovascular Events in Patients With Dilated Cardiomyopathy

Area of Science:

• Cardiology
• Biochemistry
• Pathophysiology

Background:

• Cardiac fibrosis is a key factor in dilated cardiomyopathy (DCM) development.
• Human epididymis protein 4 (HE4) is a secretory protein that promotes tissue fibrosis by activating fibroblasts.

Purpose of the Study:

• To investigate the clinical significance of HE4 levels in DCM patients.
• To explore the pathophysiological role of HE4 in cardiac fibrosis using preclinical models.

Main Methods:

• Serum HE4 levels were measured in 87 DCM patients.
• Cardiac fibrosis was assessed via endomyocardial biopsy and echocardiography.
• HE4's role in fibrosis was studied in vitro using cardiac fibroblasts and in vivo in a DCM mouse model.

Main Results:

• Higher serum HE4 levels correlated with severe cardiac fibrosis.
• Low HE4 levels were associated with improved left ventricular dimensions over time.
• HE4 significantly reduced the risk of mortality and cardiovascular hospitalization.
• In vitro studies showed HE4 enhances fibroblast activation and fibrosis-related gene expression via ERK signaling.

Conclusions:

• HE4 acts as a secretory factor that induces cardiac interstitial fibrosis by activating cardiac fibroblasts.
• HE4 shows potential as a biomarker for assessing fibrosis and as a therapeutic target in DCM.