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非靶向代谢组学为耐药性高血压的发病机制提供了新的认识。

Untargeted Metabolomics Provides Insight into the Mechanisms Underlying Resistant Hypertension.

机构信息

Department of Biopharmaceutics and Pharmacodynamics, Medical University of Gdansk, Al. Gen. J. Hallera 107, 80-416, Gdansk, Poland.

Department of Hypertension and Diabetology, Medical University of Gdansk, Debinki 7c, 80-211 Gdansk, Poland.

出版信息

Curr Med Chem. 2019;26(1):232-243. doi: 10.2174/0929867324666171006122656.

Abstract

BACKGROUND

Resistant hypertension (RH) affects about 15-20% of treated hypertensive patients worldwide. RH increases the risk of cardiovascular events such as myocardial infarction and stroke by 50%. The pathological mechanisms underlying resistance to treatment are still poorly understood.

OBJECTIVE

The main goal of this pilot study was to determine and compare plasma metabolomic profiles in resistant and non-resistant hypertensive patients.

METHODS

We applied untargeted metabolomic profiling in plasma samples collected from 69 subjects with RH and 81 subjects with controlled hypertension. To confirm patients' compliance to antihypertensive treatment, levels of selected drugs and their metabolites were determined in plasma samples with the LC-ESI-TOF/MS technique.

RESULTS

The results showed no statistically significant differences in the administration of antihypertensive drug in the compared groups. We identified 19 up-regulated and 13 downregulated metabolites in the RH.

CONCLUSION

The metabolites altered in RH are linked to oxidative stress and inflammation, endothelium dysfunction, vasoconstriction and cell proliferation. Our results may generate new hypothesis about RH development and progression.

摘要

背景

全球约有 15-20%的高血压患者为耐药性高血压(RH)。RH 会使心肌梗死和中风等心血管事件的风险增加 50%。导致治疗耐药的病理机制仍知之甚少。

目的

本初步研究的主要目标是确定并比较耐药性和非耐药性高血压患者的血浆代谢组学特征。

方法

我们应用非靶向代谢组学方法分析了 69 例 RH 患者和 81 例血压控制良好的患者的血浆样本。为了确认患者对降压治疗的依从性,我们使用 LC-ESI-TOF/MS 技术检测了血浆样本中选定药物及其代谢物的水平。

结果

结果显示,两组患者接受的降压药物治疗无统计学差异。我们在 RH 中发现了 19 个上调和 13 个下调的代谢物。

结论

RH 中改变的代谢物与氧化应激和炎症、内皮功能障碍、血管收缩和细胞增殖有关。我们的研究结果可能为 RH 的发展和进展提供新的假说。

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