@article{Zhu2025, 
author = {Xiaojun Zhu and Weidong Fei and Yusi Wang and Min Si and Yao Yao and Xiujun Han and Xiaohan Guo and Zhi Li and Peiyue Jiang},
title = {Innovative nanoparticle-based approach for preeclampsia treatment through inhibition of KAT7-mediated histone modifications},
year = {2025},
journal = {Nano Research},
volume = {18},
number = {8},
pages = {94907706},
keywords = {preeclampsia, lactylation, glycolytic metabolism, pyruvate kinase M, KAT7},
url = {https://www.sciopen.com/article/10.26599/NR.2025.94907706},
doi = {10.26599/NR.2025.94907706},
abstract = {Preeclampsia (PE) is a serious pregnancy-related disorder characterized by dysregulated glycolysis and aberrant histone lactylation in the placenta. In this study, we developed folic acid (FA)-modified lipid nanoparticles (FA-LNPs) encapsulating small interfering RNA targeting pyruvate kinase M (si-PKM), termed FA-LNP@si-PKM, to specifically modulate the molecular drivers of PE. Integrated transcriptomic and proteomic profiling identified PKM as a critical regulator in PE pathogenesis, associated with excessive lactate production and increased histone H3 lysine 18 (H3K18) lactylation. Further mechanistic studies revealed that the histone acetyltransferase lysine acetyltransferase 7 (KAT7) plays a pivotal role in mediating this lactylation process. In vitro silencing of PKM significantly reduced lactate accumulation, suppressed H3K18 lactylation, and attenuated pro-inflammatory cytokine production. Conversely, KAT7 overexpression abrogated these effects, highlighting its essential role in the PKM-lactate-H3K18la axis. In vivo, systemic administration of FA-LNP@si-PKM in an L-NAME-induced murine model of PE led to marked improvements, including reduced systolic blood pressure and proteinuria, diminished placental H3K18la levels, and lower expression of inflammatory markers IL-6 and TNF-α. These findings underscore the therapeutic potential of targeting the KAT7-H3K18la signaling axis using FA-LNP-mediated siRNA delivery. This nanotechnology-based approach offers a promising strategy for addressing the molecular etiology of PE and enhancing maternal and fetal outcomes.}
}