Citric Acid Metabolism in Resistant Hypertension: Underlying Mechanisms and Metabolic Prediction of Treatment Response.
Marta Martin-Lorenzo,Paula J. Martinez,Montserrat Baldan-Martin,Gema Ruiz-Hurtado,Jose Carlos Prado,Julian Segura,Fernando de la Cuesta,Maria G. Barderas,Fernando Vivanco,Luis M. Ruilope,Gloria Alvarez-Llamas +10 more
TLDR
In this paper, the potential capacity of metabolites to predict response to spironolactone was investigated, and a metabolic panel showing alteration before and after spironoline treatment and predicting future response of patients was shown.Abstract:
Resistant hypertension (RH) affects 9% to 12% of hypertensive adults. Prolonged exposure to suboptimal blood pressure control results in end-organ damage and cardiovascular risk. Spironolactone is the most effective drug for treatment, but not all patients respond and side effects are not negligible. Little is known on the mechanisms responsible for RH. We aimed to identify metabolic alterations in urine. In addition, a potential capacity of metabolites to predict response to spironolactone was investigated. Urine was collected from 29 patients with RH and from a group of 13 subjects with pseudo-RH. For patients, samples were collected before and after spironolactone administration and were classified in responders (n=19) and nonresponders (n=10). Nuclear magnetic resonance was applied to identify altered metabolites and pathways. Metabolites were confirmed by liquid chromatography-mass spectrometry. Citric acid cycle was the pathway most significantly altered (P<0.0001). Metabolic concentrations were quantified and ranged from ng/mL malate to μg/mL citrate. Citrate and oxaloacetate increased in RH versus pseudoresistant. Together with α-ketoglutarate and malate, they were able to discriminate between responders and nonresponders, being the 4 metabolites increased in nonresponders. Combined as a prediction panel, they showed receiver operating characteristiccurve with area under the curve of 0.96. We show that citric acid cycle and deregulation of reactive oxygen species homeostasis control continue its activation after hypertension was developed. A metabolic panel showing alteration before spironolactone treatment and predicting future response of patients is shown. These molecular indicators will contribute optimizing the rate of control of RH patients with spironolactone.read more
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Mass spectrometry-based metabolomics in health and medical science: a systematic review
TL;DR: The present review discusses the MS analysis technologies commonly used in metabolomics and the application of metabolomics in precision medicine, and further explores the challenges and perspectives of metabolismomics in the field of health and medical science.
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Impaired Autonomic Nervous System-Microbiome Circuit in Hypertension.
Jasenka Zubcevic,Elaine M. Richards,Tao Yang,Seungbum Kim,Colin Sumners,Carl J. Pepine,Mohan K. Raizada +6 more
TL;DR: In this paper, the authors synthesize some of the recent data with published reports and present concepts and a rationale for their emerging hypothesis of a dysfunctional gut-brain axis in hypertension, which will improve the understanding of hypertension and help to address some knowledge gaps.
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Emerging Applications of Metabolomics in Clinical Pharmacology.
Huanhuan Pang,Wei Jia,Zeping Hu +2 more
TL;DR: The recent advances of technologies and methodologies in metabolomics and their applications to the field of clinical pharmacology are highlighted and current challenges and potential future directions in the field are discussed.
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The metabolic fingerprints of HCV and HBV infections studied by Nuclear Magnetic Resonance Spectroscopy.
Gaia Meoni,Serena Lorini,Monica Monti,Francesco Madia,Giampaolo Corti,Claudio Luchinat,Anna Linda Zignego,Leonardo Tenori,Laura Gragnani +8 more
TL;DR: This metabolomic study evaluating a group of HCV-positive patients, before and after viral eradication via DAA IFN-free regimens, using 1H-NMR to characterize and compare their serum fingerprints to naïve HBV-patients and healthy donors confirms the hypothesis that the metabolic perturbation on patients could be attributed to a direct role in viral infection.
Journal ArticleDOI
Diagnosis and management of resistant hypertension: state of the art.
Fang-Fei Wei,Zhenyu Zhang,Zhenyu Zhang,Qi-Fang Huang,Qi-Fang Huang,Jan A. Staessen,Jan A. Staessen +6 more
TL;DR: Device treatment remains a last-resort for patients with truly resistant hypertension in the context of clinical research in highly skilled tertiary referral centres and future research should focus on improving understanding of the intrinsic and extrinsic mechanisms that contribute to a lack of response to blood-pressure-lowering drugs in adherent patients.
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