Modulating Placental Functionality in Preeclampsia With siRNA Nanocomplexes.

IF 8.2 1区医学 Q1 PERIPHERAL VASCULAR DISEASE

Hypertension Pub Date : 2025-09-11 DOI:10.1161/hypertensionaha.124.24291

Xue Peng,Xi Tan,Li Dai,Wei Xia,Zhao Wu

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Abstract

BACKGROUND Early-onset preeclampsia poses significant risks to maternal and fetal health, necessitating a deeper understanding of its molecular mechanisms and effective therapeutic strategies. METHODS Utilizing data from genome-wide association study and Mendelian randomization analysis, we investigated the relationship between mitochondrial DNA copy number and preeclampsia. Transcriptome sequencing, in vitro experiments, and animal studies were conducted to explore the roles of SENP3 and SETD7 in preeclampsia pathogenesis. The development and evaluation of siRNA SENP3 delivered by DMD@DPF nanoparticles as a potential therapeutic intervention were also performed. RESULTS Our findings revealed a negative correlation between mitochondrial DNA copy number and preeclampsia, significant differential expression of SENP3 and SETD7 in preeclampsia placentas, and the therapeutic effects of siRNA SENP3 delivered by DMD@DPF nanoparticles on physiological parameters in a preeclampsia mouse model. CONCLUSIONS This study highlights the crucial involvement of SENP3 and SETD7 in preeclampsia pathophysiology and proposes siRNA SENP3 delivered by DMD@DPF nanoparticles as a promising therapeutic approach for preeclampsia treatment.

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用siRNA纳米复合物调节子痫前期胎盘功能。

背景早发型子痫前期对母婴健康有重大风险，需要对其分子机制和有效治疗策略有更深入的了解。方法利用全基因组关联研究和孟德尔随机化分析的数据，探讨线粒体DNA拷贝数与子痫前期的关系。通过转录组测序、体外实验和动物实验，探讨SENP3和SETD7在子痫前期发病中的作用。研究人员还对DMD@DPF纳米颗粒递送siRNA SENP3作为一种潜在的治疗干预手段进行了开发和评估。结果我们的研究结果揭示了线粒体DNA拷贝数与子痫前期存在负相关，SENP3和SETD7在子痫前期胎盘中的表达存在显著差异，DMD@DPF纳米颗粒递送siRNA SENP3对子痫前期小鼠模型生理参数的治疗作用。本研究强调了SENP3和SETD7在子痫前期病理生理中的重要作用，并提出了DMD@DPF纳米颗粒递送的siRNA SENP3作为子痫前期治疗的一种有前景的治疗方法。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Hypertension 医学-外周血管病

CiteScore

15.90

自引率

4.80%

发文量

1006

审稿时长

1 months

期刊介绍： Hypertension presents top-tier articles on high blood pressure in each monthly release. These articles delve into basic science, clinical treatment, and prevention of hypertension and associated cardiovascular, metabolic, and renal conditions. Renowned for their lasting significance, these papers contribute to advancing our understanding and management of hypertension-related issues.