# Lactylering van BCAT2-K377 draagt bij aan ernstige pre-eclampsie

*geplaatst 2026-02-17 · Hypertensie · Hypertension · doi https://www.ahajournals.org/doi/abs/10.1161/HYPERTENSIONAHA.125.25378 · https://hartvaat.nl/2026/02/17/lactylering-van-bcat2-k377-draagt-bij-aan-ernstige-pre-eclampsie/*

Pre-eclampsie wordt gekenmerkt door placentaire hypoxie en oppervlakkige trofoblastinvasie. Dit onderzoek toont aan dat hypoxie-geïnduceerde lactylering van BCAT2 een nieuw mechanisme is dat bijdraagt aan de progressie van ernstige pre-eclampsie.

## English: Lactylation of BCAT2-K377 Contributes to the Progression of Severe Preeclampsia

This study reveals that hypoxia-induced lactylation of BCAT2 at K377 is a novel mechanism contributing to severe preeclampsia progression, linking metabolic reprogramming under placental hypoxia to trophoblast dysfunction.

## Abstract (original, from the publication)

Hypertension, Volume 83, Issue 6, Page e25378, June 1, 2026. BACKGROUND:Preeclampsia is a pregnancy-specific disorder characterized by placental hypoxia and superficial invasion of trophoblast cells. However, the precise mechanisms by which hypoxia induces lactate and lactylation remain unclear.METHODS:Pan lysine lactylation levels were analyzed in the placentae of 36 patients with severe preeclampsia (sPE) and 36 normotensive pregnancies. A global lactylome analysis was performed, and branched-chain amino acid transaminase 2-lysine 377 (BCAT2-K377) was selected for further investigation. The BCAT2 mutant with lysine 377 mutated to arginine (BCAT2-377R) was constructed to evaluate the effect on trophoblast migration, invasion, tube formation, and oxidative stress. The impact of the BCAT2-377R mutant on BCAT2 ubiquitination and degradation was further examined using MG132 and cycloheximide supplementation. Co-immunoprecipitation and double-immunofluorescence staining were conducted to identify the lactyltransferase of BCAT2. The specialized antibody was developed to validate branched-chain amino acid transaminase 2-lysine 377 lactylation (BCAT2-K377la) abundance in tissues and treated cells. A preeclampsia-like rat model was constructed to further verify whether the results were consistent with the clinical findings.RESULTS:Lactylation levels were elevated in the placentae of sPE. High lactate concentration enhanced Pan lysine lactylation and reduced BCAT2 protein levels while inhibiting cell migration, invasion, and tube formation. BCAT2-K377la impaired cell biological behaviors, increased oxidative stress, and promoted BCAT2 ubiquitination. The EP300 lysine acetyltransferase (p300) acted as a lysine lactylation writer of BCAT2. BCAT2-K377la abundance was upregulated in sPE placentae and cells treated with hypoxia and lactate. In the rat model, elevated placental Pan lysine lactylation and BCAT2-K377la levels mirrored findings in clinical samples.CONCLUSIONS:Our findings emphasized the role of nonhistone lactylation in sPE pathogenesis. Targeting BCAT2-K377la may serve as a potential intervention strategy for sPE.

Auteurs: Yangxue Yin

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Bron: Hypertension, https://doi.org/https://www.ahajournals.org/doi/abs/10.1161/HYPERTENSIONAHA.125.25378. Bijgewerkt 2026-07-03T13:24:46Z. Citeer vrij, met bronvermelding en een link naar hartvaat.nl (de url van het record). Samenvattingen zijn redactioneel werk van HartVaat; de oorspronkelijke publicaties blijven van hun uitgevers (doi). Geen medisch advies.