Dataset Information

Circulating metabolomics profiling reveals novel pathways associated with cognitive decline in patients with hypertension.

ABSTRACT:

Background

Hypertension is a significant risk factor for cardiovascular disease, and it is associated with dementia, including Alzheimer's disease (AD). Although it may be correlated with AD in terms of symptoms, the link between hypertension and AD pathological biomarkers, and the potential underlying mechanism of hypertension with cognitive decline, are still not well understood.

Methods

The Mini-Mental State Examination (MMSE) scores were used to evaluate cognitive function. Enzyme-linked immunosorbent assays were used to examine plasma amyloid-beta (Aβ)₄₀, Aβ₄₂, and tau concentration in hypertensive patients. Metabolomics and metagenomics were performed to identify the significantly changed circulating metabolites and microbiota between healthy individuals and hypertensive patients. Pearson's correlation was used to examine the association between cognitive indicators and differential metabolites.

Results

We found significantly decreased MMSE scores, elevated plasma Aβ₄₀, and decreased Aβ₄₂/Aβ₄₀ ratio in hypertensive patients, which are critically associated with AD pathology. Based on metabolomics, we found that significantly altered metabolites in the plasma of hypertensive patients were enriched in the benzoate degradation and phenylpropanoid biosynthesis pathways, and they were also correlated with changes in MMSE scores and Aβ₄₂/Aβ₄₀ ratio. In addition, metabolomics signaling pathway analysis suggested that microbial metabolism was altered in hypertensive patients. We also identified altered blood microbiota in hypertensive patients compared with the controls.

Conclusions

Our study provides a novel metabolic and microbial mechanism, which may underlie the cognitive impairment in hypertensive patients.

SUBMITTER: Huang Y

PROVIDER: S-EPMC7476355 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Publications

Circulating metabolomics profiling reveals novel pathways associated with cognitive decline in patients with hypertension.

Huang Yuli Y Zheng Haoxiao H Tan Kuan K Sun Xiangdong X Ye Jinshao J Zhang Yunlong Y

Therapeutic advances in neurological disorders 20200903

<h4>Background</h4>Hypertension is a significant risk factor for cardiovascular disease, and it is associated with dementia, including Alzheimer's disease (AD). Although it may be correlated with AD in terms of symptoms, the link between hypertension and AD pathological biomarkers, and the potential underlying mechanism of hypertension with cognitive decline, are still not well understood.<h4>Methods</h4>The Mini-Mental State Examination (MMSE) scores were used to evaluate cognitive function. En ...[more]

PMID: 32952614

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Project description:Yams are economic and medicinal crops with a long growth cycle, spanning between 9-11 months due to their prolonged tuber dormancy. Tuber dormancy has constituted a major constraint in yam production and genetic improvement. In this study, we performed non-targeted comparative metabolomic profiling of tubers of two white yam genotypes, (Obiaoturugo and TDr1100873), to identify metabolites and associated pathways that regulate yam tuber dormancy using gas chromatography-mass spectrometry (GC-MS). Yam tubers were sampled between 42 days after physiological maturity (DAPM) till tuber sprouting. The sampling points include 42-DAPM, 56-DAPM, 87DAPM, 101-DAPM, 115-DAPM, and 143-DAPM. A total of 949 metabolites were annotated, 559 in TDr1100873 and 390 in Obiaoturugo. A total of 39 differentially accumulated metabolites (DAMs) were identified across the studied tuber dormancy stages in the two genotypes. A total of 27 DAMs were conserved between the two genotypes, whereas 5 DAMs were unique in the tubers of TDr1100873 and 7 DAMs were in the tubers of Obiaoturugo. The differentially accumulated metabolites (DAMs) spread across 14 major functional chemical groups. Amines and biogenic polyamines, amino acids and derivatives, alcohols, flavonoids, alkaloids, phenols, esters, coumarins, and phytohormone positively regulated yam tuber dormancy induction and maintenance, whereas fatty acids, lipids, nucleotides, carboxylic acids, sugars, terpenoids, benzoquinones, and benzene derivatives positively regulated dormancy breaking and sprouting in tubers of both yam genotypes. Metabolite set enrichment analysis (MSEA) revealed that 12 metabolisms were significantly enriched during yam tuber dormancy stages. Metabolic pathway topology analysis further revealed that six metabolic pathways (linoleic acid metabolic pathway, phenylalanine metabolic pathway, galactose metabolic pathway, starch and sucrose metabolic pathway, alanine-aspartate-glutamine metabolic pathways, and purine metabolic pathway) exerted significant impact on yam tuber dormancy regulation. This result provides vital insights into molecular mechanisms regulating yam tuber dormancy.

Project description:BackgroundPulmonary hypertension and associated right ventricular (RV) dysfunction are important determinants of morbidity and mortality, which are optimally characterized by invasive hemodynamic measurements.ObjectivesThis study sought to determine whether metabolite profiling could identify plasma signatures of right ventricular-pulmonary vascular (RV-PV) dysfunction.MethodsWe measured plasma concentrations of 105 metabolites using targeted mass spectrometry in 71 individuals (discovery cohort) who underwent comprehensive physiological assessment with right-sided heart catheterization and radionuclide ventriculography at rest and during exercise. Our findings were validated in a second cohort undergoing invasive hemodynamic evaluations (n = 71), as well as in an independent cohort with or without known pulmonary arterial (PA) hypertension (n = 30).ResultsIn the discovery cohort, 21 metabolites were associated with 2 or more hemodynamic indicators of RV-PV function (i.e., resting right atrial pressure, mean PA pressure, pulmonary vascular resistance [PVR], and PVR and PA pressure-flow response [ΔPQ] during exercise). We identified novel associations of RV-PV dysfunction with circulating indoleamine 2,3-dioxygenase (IDO)-dependent tryptophan metabolites (TMs), tricarboxylic acid intermediates, and purine metabolites and confirmed previously described associations with arginine-nitric oxide metabolic pathway constituents. IDO-TM levels were inversely related to RV ejection fraction and were particularly well correlated with exercise PVR and ΔPQ. Multisite sampling demonstrated transpulmonary release of IDO-TMs. IDO-TMs also identified RV-PV dysfunction in a validation cohort with known risk factors for pulmonary hypertension and in patients with established PA hypertension.ConclusionsMetabolic profiling identified reproducible signatures of RV-PV dysfunction, highlighting both new biomarkers and pathways for further functional characterization.

Dataset Information

Circulating metabolomics profiling reveals novel pathways associated with cognitive decline in patients with hypertension.

Background

Methods

Results

Conclusions

Publications

Circulating metabolomics profiling reveals novel pathways associated with cognitive decline in patients with hypertension.

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