Endothelial Cell Dysfunction and Retinal Arteriolar Narrowing in Young Adults With Elevated Blood Pressure
Bibliographic record
Abstract
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
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot 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.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
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".