Cardiomyocyte-Derived Apelin Rescues Viral Myocarditis-Induced Cardiac Lymphatic Dysfunction and Remodeling

Area of Science:

• Cardiovascular Biology
• Lymphatic System Research
• Virology

Background:

• Cardiac lymphatic vessels (CLVs) are crucial for resolving inflammation.
• The role of CLVs in coxsackievirus B3-induced acute viral myocarditis (AVMC) is not well understood.

Purpose of the Study:

• To investigate the function of CLVs in AVMC.
• To explore the therapeutic potential of apelin in improving CLV function during AVMC.

Main Methods:

• AVMC was induced in mice.
• Cardiac lymphangiogenesis and drainage were assessed.
• Apelin was overexpressed in cardiomyocytes.
• In vitro studies examined apelin's effect on lymphatic endothelial cell junctions and signaling pathways.
• Vascular endothelial growth factor receptor 3 (VEGFR3) was blocked to assess lymphatic defects.

Main Results:

• AVMC led to pathological cardiac lymphangiogenesis and impaired CLV drainage, causing heart inflammation and dysfunction.
• Apelin overexpression in cardiomyocytes enhanced CLV integrity and drainage, reducing inflammation and improving cardiac function.
• Apelin stabilized lymphatic endothelial cadherin and zonula occludens 1 via the AKT signaling pathway in vitro.
• Pre-existing lymphatic defects partially negated the benefits of apelin overexpression.

Conclusions:

• Functional CLVs, restored by cardiomyocyte-derived apelin, facilitate inflammation resolution and improve cardiac function in AVMC.
• CLV-based therapeutic strategies show promise for treating AVMC-associated heart damage.