【Paper】Science Advances

This is a collaborative research paper with Prof. Yokoi. We demonstrated that placenta-derived extracellular vesicles (EVs) enriched in LIMCH1, which are elevated in the serum of patients with early-onset preeclampsia (Eo-PE), contribute to disease pathogenesis by downregulating the tight junction protein ZO-1 in vascular endothelial cells, thereby disrupting endothelial barrier function and increasing vascular permeability.

Paper overview
Early-onset preeclampsia (Eo-PE) is a severe pregnancy complication that develops before 34 weeks of gestation and is characterized by maternal hypertension, proteinuria, and systemic endothelial dysfunction. However, its molecular mechanisms—particularly how placenta-derived factors affect maternal vascular function—have not been fully elucidated. In this study, we focused on extracellular vesicles (EVs) in the serum of patients with Eo-PE and performed an integrated analysis combining EV proteomics and RNA sequencing of placental tissues to identify disease-associated EV cargo proteins. As a result, LIM and calponin homology domain–containing protein 1 (LIMCH1) was identified as a molecule specifically enriched in EVs derived from patients with Eo-PE. LIMCH1 was highly expressed in syncytiotrophoblasts of the placenta, and its levels in circulating EVs were significantly elevated in Eo-PE cases. Functional analyses revealed that treatment of vascular endothelial cells with LIMCH1-enriched EVs reduced the expression of the tight junction protein ZO-1 and disrupted intercellular junctional structures. Consequently, endothelial barrier function was impaired, leading to increased vascular permeability. Furthermore, administration of these EVs in an animal model induced enhanced pulmonary vascular permeability, demonstrating that LIMCH1-containing EVs impair vascular barrier function in vivo. These findings suggest that placenta-derived LIMCH1-enriched EVs are released into the maternal circulation and contribute to the pathogenesis of Eo-PE by inducing systemic endothelial dysfunction. This study provides a new molecular basis for increased vascular permeability in Eo-PE and highlights the potential of LIMCH1-containing EVs as biomarkers for disease severity and as therapeutic targets.

Publication Information
LIMCH1-enriched extracellular vesicles promote vascular permeability in early-onset preeclampsia
S. Matsuo, A. Yokoi*, T. Ushida, K. Yoshida, H. Suzuki, M. Kitagawa, E. Asano-Inami, H. Yamada, R. Miki, S. Tano, K. Imai, I. Nagata, S. Kawaguchi, T. Yasui, Y. Yamamoto, H. Kajiyama and T. Kotani
Sci. Adv., 12, eaeb8806 (2026)
https://doi.org/10.1126/sciadv.aeb8806

Science Advances
Science Advances is a peer-reviewed, open-access multidisciplinary journal published by the American Association for the Advancement of Science (AAAS). It covers a broad range of fields across the natural and applied sciences, from fundamental research to engineering, life sciences, environmental sciences, and social sciences, and aims to rapidly disseminate innovative, high-impact research to the global scientific community.