Untargeted Metabolomics Provides Insight into the Mechanisms Underlying Resistant Hypertension

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Author(s): Renata Bujak, Arlette Yumba-Mpanga, Wiktoria Struck-Lewicka, Marta Kordalewska, Katarzyna Polonis, Małgorzata Patejko, Monika Mironiuk, Anna Szyndle, Marzena Chrostowska, Michał Hoffmann, Ryszard T. Smoleński, Roman Kaliszan, Krzysztof Narkiewicz, Michał J. Markuszewski*.

Journal Name: Current Medicinal Chemistry

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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. Method: 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 of antihypertensive drug administration in the compared groups. We identified 19 up-regulated and 13 down-regulated metabolites in 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.

Keywords: resistant hypertension, metabolomics, liquid chromatography mass spectrometry, multivariate analysis, biomarker candidates.

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(E-pub Ahead of Print)
DOI: 10.2174/0929867324666171006122656

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