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Untargeted Metabolomics Provides Insight into the Mechanisms Underlying Resistant Hypertension

[ Vol. 26 , Issue. 1 ]

Author(s):

Renata Wawrzyniak, Arlette Yumba Mpanga, Wiktoria Struck-Lewicka, Marta Kordalewska, Katarzyna Polonis, Małgorzata Patejko, Monika Mironiuk, Anna Szyndler, Marzena Chrostowska, Michał Hoffmann, Ryszard T. Smoleński, Roman Kaliszan, Krzysztof Narkiewicz and Michał J. Markuszewski*   Pages 232 - 243 ( 12 )

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.

Keywords:

Resistant hypertension, metabolomics, liquid chromatography, mass spectrometry, multivariate analysis, biomarker candidates.

Affiliation:

Department of Biopharmaceutics and Pharmacodynamics, Medical University of Gdansk, Al. Gen. J. Hallera 107, 80-416, Gdansk, Department of Biopharmaceutics and Pharmacodynamics, Medical University of Gdansk, Al. Gen. J. Hallera 107, 80-416, Gdansk, Department of Biopharmaceutics and Pharmacodynamics, Medical University of Gdansk, Al. Gen. J. Hallera 107, 80-416, Gdansk, Department of Biopharmaceutics and Pharmacodynamics, Medical University of Gdansk, Al. Gen. J. Hallera 107, 80-416, Gdansk, Department of Hypertension and Diabetology, Medical University of Gdansk, Debinki 7c, 80-211 Gdansk, Department of Biopharmaceutics and Pharmacodynamics, Medical University of Gdansk, Al. Gen. J. Hallera 107, 80-416, Gdansk, Department of Biopharmaceutics and Pharmacodynamics, Medical University of Gdansk, Al. Gen. J. Hallera 107, 80-416, Gdansk, Department of Hypertension and Diabetology, Medical University of Gdansk, Debinki 7c, 80-211 Gdansk, Department of Hypertension and Diabetology, Medical University of Gdansk, Debinki 7c, 80-211 Gdansk, Department of Hypertension and Diabetology, Medical University of Gdansk, Debinki 7c, 80-211 Gdansk, Department of Biochemistry, Medical University of Gdansk, Debinki 1, 80-211 Gdansk, Department of Biopharmaceutics and Pharmacodynamics, Medical University of Gdansk, Al. Gen. J. Hallera 107, 80-416, Gdansk, Department of Hypertension and Diabetology, Medical University of Gdansk, Debinki 7c, 80-211 Gdansk, Department of Biopharmaceutics and Pharmacodynamics, Medical University of Gdansk, Al. Gen. J. Hallera 107, 80-416, Gdansk



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