March 3, 2026Open Access

LIMCH1-enriched extracellular vesicles promote vascular permeability in early-onset preeclampsia

Puntos clave

LIMCH1-enriched extracellular vesicles promote endothelial permeability, indicating a role in vascular dysfunction.
In vitro analysis showed a disruption of tight junction protein ZO-1 expression by LIMCH1-extracellular vesicles.
Transcriptome analysis revealed mechanisms by which LIMCH1-EVs affect endothelial cell-cell junction assembly.
Findings highlight LIMCH1 as a potential therapeutic target in managing preeclampsia-associated complications.

Resumen

Preeclampsia (PE) is a major pregnancy complication characterized by hypertension and multiple end-organ dysfunctions; however, its detailed pathogenesis remains unclear. Extracellular vesicles (EVs) play diverse and critical roles in intercellular communication, and we have demonstrated interaction between EVs and vascular endothelial cells. Through serum proteomic analysis, we identified LIM and calponin homology domain-containing protein 1 (LIMCH1) as a PE-associated EV protein that is highly expressed in PE placentas, particularly in syncytiotrophoblasts, which release EVs into the maternal circulation. LIMCH1-enriched EVs (LIMCH1-EVs) increased endothelial permeability in vitro. Transcriptome analysis revealed that LIMCH1-EVs disrupted endothelial cell-cell junction assembly by suppressing the expression of the tight junction protein ZO-1. Furthermore, administration of LIMCH1-EVs promoted pulmonary vascular permeability in vivo. These findings suggest a role of LIMCH1-EVs in EV-associated vascular endothelial dysfunction, a central pathology of PE. In addition, this study provides insights into mechanisms that may contribute to PE-associated pulmonary edema, which have not yet been clarified.

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