Heart Failure Pleural Fluid Impairs Endothelial Barrier through miR 501-3p Mediated ZO 1 Remodeling

Summary: Heart failure is frequently accompanied by pleural effusion, yet the biological impact of heart failure–associated pleural fluid on vascular endothelial function remains unclear. Here, we show that heart failure 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, heart failure 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 heart failure pleural fluid to endothelial dysfunction and suggest a potential molecular pathway contributing to vascular complications in heart failure.