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Record W4400814990 · doi:10.1101/2024.07.12.603349

Endothelial Cell Dysfunction and Retinal Arteriolar Narrowing in Young Adults With Elevated Blood Pressure

2024· preprint· en· W4400814990 on OpenAlexaff
Cheryl Tan, Adam J. Lewandowski, Henner Hanssen, Lukas Streese, Odaro J. Huckstep, Román Fischer, Maryam Alsharqi, Afifah Mohamed, Wilby Williamson, Paul Leeson, Mariane Bertagnolli

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2024
Typepreprint
Languageen
FieldMedicine
TopicRetinal and Optic Conditions
Canadian institutionsMcGill University Health CentreMcGill UniversityDiscovery Centre
Fundersnot available
KeywordsBlood pressureRetinalCardiologyEndothelial dysfunctionMedicineInternal medicineOphthalmology

Abstract

fetched live from OpenAlex

ABSTRACT Background Young-adults with endothelial cell dysfunction are more likely to develop elevated blood pressure. We tested the hypothesis that this relates to development of structural microvascular impairments by studying associations between circulating endothelial colony-forming cell (ECFC) dysfunction and microvascular markers, as well as identifying related endothelial molecular mechanisms. Methods Peripheral blood ECFCs were isolated from 32 subjects (53% men, 28±4 years old) using the Ficoll density gradient centrifugation method. Participants with blood pressure ≥120/80 mm Hg were included in the elevated blood pressure (BP) group, whereas ≤120/80 mm Hg were classed as normotensive. Retinal microvasculature was assessed by Static Retinal Vessel Analyzer (SVA-T). Results Subjects with elevated BP had impaired in vitro ECFC colony-forming growth, cell proliferation and angiogenesis assessed by tube formation potential. There was a graded inverse association between ECFC colony-forming capacity (days taken for ECFC colony growth) and retinal arteriolar diameter, as well as arteriolar/venular ratio. Proteomic analysis of ECFCs identified differences in extracellular matrix organization, blood coagulation, exocytosis and vesicle transport proteins in subjects with elevated blood pressure, revealing the adaptor protein GRB2 as a potential link between endothelial cell and microvascular abnormalities. Conclusions Endothelial cell dysfunction associates with retinal arteriolar narrowing in men and women with elevated blood pressure. Endothelial molecular mechanisms linked to reduced adaptive postnatal angiogenesis capacity, rather than vascular development, may contribute to early microvascular changes. HIGHLIGHTS Subjects with elevated blood pressure had impaired in vitro endothelial cell growth and angiogenesis in comparison to normotensive subjects. There was an association between impaired endothelial cell growth capacity and reduced retinal arteriolar diameter. Different endothelial proteome signatures were identified, revealing the adaptor protein GRB2 as a potential link between endothelial and microvascular abnormalities in subjects with elevated blood pressure. GRAPHICAL ABSTRACT

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 distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.567
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0000.000

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 head0.005
GPT teacher head0.191
Teacher spread0.186 · 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 teacher head, not a consensus.

Study designBench or experimental
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
Published2024
Admission routes1
Has abstractyes

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