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

Yuan-Nan Lin1, Jing Xu1, Yi-Hao Wu1

  • 1Department of Cardiology, Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.

JACC. Basic to Translational Science
|April 28, 2026
PubMed

Insights

Coxsackievirus B3-induced acute viral myocarditis impairs cardiac lymphatic vessels (CLVs). Apelin overexpression in heart cells improves CLV function, reducing inflammation and enhancing cardiac repair in this viral myocarditis model.

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.

Keywords:
apelincardiac lymphangiogenesisdrainageinflammationviral myocarditis

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