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

TL;DR

This study shows that extracellular vesicles enriched with LIMCH1 increase blood vessel permeability, contributing to the development of preeclampsia.

Contribution

The study identifies LIMCH1 as a novel PE-associated EV protein that disrupts endothelial junctions and promotes vascular permeability.

Findings

LIMCH1 is highly expressed in PE placentas and released via EVs into maternal circulation.

LIMCH1-EVs increase endothelial permeability by suppressing ZO-1 expression in vitro.

Administration of LIMCH1-EVs promotes pulmonary vascular permeability in vivo.

Abstract

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.

LIMCH1-enriched extracellular vesicles promote endothelial permeability, which is a central pathology of preeclampsia.

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