Wang Shanshan, Hu Yuanlong, Wang Yuqi, Song Yueyue, Liang Dan, Yin Jiufeng, Li Yunlun, Yang Wenqing, Zhang Dan
Innovative Institute of Chinese Medicine and Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, China.
Department of Cardiology, The Fifth People's Hospital of Jinan, Jinan, China.
J Clin Hypertens (Greenwich). 2025 Jan;27(1):e14961. doi: 10.1111/jch.14961. Epub 2024 Dec 24.
Resistant hypertension (RH) may cause severe target organ damage and poses significant challenges in the field of hypertension prevention and treatment. Mining biological characteristics is crucial for exploring the pathogenesis of RH and for early diagnosis and treatment. Although several single-omics studies have been conducted on RH, its complex pathogenesis has only been partially elucidated. In this study, metabolomics, proteomics, and transcriptomics were jointly analyzed in healthy subjects and patients with hypertension and RH. The multi-omics analysis found that differential substances of RH were enriched in the HIF-1 signaling pathway and that differential substances such as ascorbic acid, reduced glutathione (GSH), choline, citric acid, transferrin receptor (TfR), Egl-9 family hypoxia-inducible factor 2 (EGLN2), and glutathione peroxidase 1 (GPX1) were screened out. The results of intergroup comparisons were as follows: RH versus N: ascorbic acid (Fold Change (FC):0.42, p < 0.01), GSH (FC:0.65, p < 0.05), choline (FC:1.32, p < 0.05), citric acid (FC:0.48, p < 0.001), TfR (FC2.32, p < 0.001), GPX1 (FC:16.02, p < 0.001), EGLN2 (FC:0.76, p < 0.001); RH versus EH: ascorbic acid (FC:0.52, p < 0.05), GSH (FC:0.55, p < 0.05), choline (FC:1.28, p < 0.05), citric acid (FC:0.59, p < 0.001), TfR (FC:1.71, p < 0.001), GPX1 (FC:2.11, p < 0.05), EGLN2 (FC:0.76, p < 0.05). These differential substances may reflect the biology of RH. This study provides multi-omics analysis for a deeper understanding of the complex molecular characteristics of RH, providing new insights into the pathogenesis, early diagnosis, and precise treatment of the disease.
难治性高血压（RH）可导致严重的靶器官损害，给高血压防治领域带来重大挑战。挖掘生物学特征对于探究RH的发病机制以及早期诊断和治疗至关重要。尽管已经针对RH开展了多项单组学研究，但其复杂的发病机制仅得到部分阐明。在本研究中，对健康受试者、高血压患者和RH患者联合进行了代谢组学、蛋白质组学和转录组学分析。多组学分析发现，RH的差异物质在缺氧诱导因子-1（HIF-1）信号通路中富集，并且筛选出了诸如抗坏血酸、还原型谷胱甘肽（GSH）、胆碱、柠檬酸、转铁蛋白受体（TfR）、Egl-9家族缺氧诱导因子2（EGLN2）和谷胱甘肽过氧化物酶1（GPX1）等差异物质。组间比较结果如下：RH组与正常组相比：抗坏血酸（倍数变化（FC）：0.42，p < 0.01），GSH（FC：0.65，p < 0.05），胆碱（FC：1.32，p < 0.05），柠檬酸（FC：0.48，p < 0.001），TfR（FC：2.32，p < 0.001），GPX1（FC：16.02，p < 0.001），EGLN2（FC：0.76，p < 0.001）；RH组与原发性高血压（EH）组相比：抗坏血酸（FC：0.52，p < 0.05），GSH（FC：0.55，p < 0.05），胆碱（FC：1.28，p < 0.05），柠檬酸（FC：0.59，p < 0.001），TfR（FC：1.71，p < 0.001），GPX1（FC：2.11，p < 0.05），EGLN2（FC：0.76，p < 0.05）。这些差异物质可能反映了RH的生物学特性。本研究提供了多组学分析，以更深入地了解RH复杂的分子特征，为该疾病的发病机制、早期诊断和精准治疗提供了新的见解。
