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Record W4389795093 · doi:10.1101/2023.12.14.23299991

Association of urinary peptides with hypertension

2023· preprint· en· W4389795093 on OpenAlexaff
Emmanouil Mavrogeorgis, Margarita Kondyli, Harald Mischak, Antonia Vlahou, Justyna Siwy, Peter Rossing, Archie Campbell, Catharina M. C. Mels, Christian Delles, Jan A. Staessen, Agnieszka Latosińska, Alexandre Persu

Bibliographic record

VenuemedRxiv · 2023
Typepreprint
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicProtein Hydrolysis and Bioactive Peptides
Canadian institutionsHealth Sciences North
Fundersnot available
KeywordsCohortBlood pressureMedicineBody mass indexPathophysiologyUrinary systemInternal medicinePopulationCohort studyEndocrinologyDiabetes mellitusEssential hypertensionBioinformaticsPhysiologyBiologyEnvironmental health

Abstract

fetched live from OpenAlex

Abstract BACKGROUND Hypertension is a common condition worldwide, yet its underlying mechanisms remain largely unknown. This study aims at identifying urinary peptides associated with hypertension to further explore its molecular pathophysiology. METHODS Peptidome data from 2876 individuals without end-organ damage were retrieved from the Human Urinary Proteome Database general population (discovery) or type 2 diabetic (validation) cohorts. Participants were divided based on systolic and diastolic blood pressure (SBP and DBP) into hypertensive (SBP≥140mmHg and/or DBP≥90mmHg) and normotensive (SBP<120mmHg and DBP<80mmHg, without antihypertensive treatment) groups. Differences in peptide abundance between the two groups were confirmed using an external cohort (n=420) of participants without end-organ damage, matched for age, body-mass index, eGFR, sex and presence of diabetes. Further, associations of the peptides with BP as a continuous variable were investigated. Findings were compared with peptide biomarkers of chronic diseases and bioinformatics analyses were conducted to potentially highlight the underlying molecular mechanisms. RESULTS Between hypertensive and normotensive individuals, ninety-six (mostly COL1A1 and COL3A1) peptides were found significantly different in the discovery (adjusted) as well as the validation (nominal significance) cohorts with consistent regulation. Of these peptides, 83 were also consistently regulated in the matched cohort. A weak, yet significant association between their abundance and standardized BP was also observed. CONCLUSIONS Hypertension is associated with an altered urinary peptide profile, with evident collagen differential regulation. Peptides related to vascular calcification and sodium regulation are also affected. Whether these modifications reflect the pathophysiology of hypertension per se and/or early subclinical target organ damage warrants further investigation. Novelty and Relevance What is New? This is the first study demonstrating differential regulation of urinary peptides in hypertensive patients, independent from other co-factors like age, diabetes, or established kidney or cardiovascular disease. What is Relevant? The observed changes in urinary peptides indicate individual differences in molecular changes observed in hypertension, and may guide personalized treatment based on the observed molecular changes Clinical/Pathophysiological Implications? The results indicate that collagen homeostasis may be a key molecular feature in hypertension and may serve as an attractive mechanism for pharmacological intervention.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.001
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.002
Threshold uncertainty score0.006

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.001
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0020.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.021
GPT teacher head0.243
Teacher spread0.222 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations0
Published2023
Admission routes1
Has abstractyes

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