2. Academic Validation
  3. Heart failure pleural fluid impairs endothelial barrier through miR 501-3p mediated ZO 1 remodeling

Heart failure pleural fluid impairs endothelial barrier through miR 501-3p mediated ZO 1 remodeling

  • iScience. 2026 Apr 2;29(5):115549. doi: 10.1016/j.isci.2026.115549.
Chieh-Yung Wang 1 2,  Tung-Yu Tiong 3 4,  Ying Chen 5,  Yi-Hsuan Lin 5,  Vijesh Kumar Yadav 3 4,  Chih-Ying Changchien 6,  Chih-Feng Chian 2,  Chen-Liang Tsai 2 7 8
Affiliations

Affiliations

  • 1 Department of Internal Medicine, Tri-Service General Hospital Penghu Branch, National Defense Medical University, Taipei, Taiwan.
  • 2 Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical University, Taipei, Taiwan.
  • 3 Division of Thoracic Surgery, Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan.
  • 4 Division of Thoracic Surgery, Department of Surgery, Taipei Medical University-Shuang Ho Hospital, New Taipei City 235, Taiwan.
  • 5 Graduate Institute of Biology and Anatomy, collage of medicine, National Defense Medical University, Taipei, Taiwan.
  • 6 Division of Rheumatology, Immunology and Allergy, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical University, Taipei, Taiwan.
  • 7 Department of Critical Care Medicine, Tri-Service General Hospital, National Defense Medical University, Taipei, Taiwan, Republic of China.
  • 8 Department of Internal Medicine, School of Medicine, College of Medicine, National Defense Medical University, Taipei, Taiwan.
PMID: 42058897 DOI: 10.1016/j.isci.2026.115549
Abstract

Heart failure (HF) is frequently accompanied by pleural effusion, yet the biological impact of HF-associated pleural fluid on vascular endothelial function remains unclear. Here, we show that HF pleural fluid impairs endothelial barrier integrity and angiogenic capacity in human umbilical vein endothelial cells. Functional assays revealed increased permeability, reduced migration, and altered tube formation following treatment with patient-derived pleural fluid. Mechanistically, HF pleural fluid increased Reactive Oxygen Species production and inflammatory signaling while downregulating tight junction protein ZO-1. Small RNA profiling identified miR-501-3p as a key mediator of these effects. Gain- and loss-of-function experiments demonstrated that miR-501-3p directly regulates ZO-1 expression and contributes to barrier disruption. These findings establish a microRNA-dependent mechanism linking HF pleural fluid to endothelial dysfunction and suggest a potential molecular pathway contributing to vascular complications in HF.

Keywords

biochemical mechanism; biological sciences; health sciences; molecular mechanism of gene regulation.

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