Extracellular-Nitric Oxide-Mediated Platelet-cGMP Production in Type 2 Diabetics Correlates Inversely with Plasma Membrane Cholesterol Levels
Bibliographic record
Abstract
Recently, we showed that the diffusion of nitric oxide (NO) and NO-mediated signaling was affected by the levels of plasma membrane cholesterol in fibroblasts [1].The generality of these observations, which would imply that perturbations in NO-signaling mediated by increased membrane cholesterol levels, could be a common pathological trigger in vascular cells, was tested in platelets from normal and dyslipidemic type 2 diabetic (T2D) subjects.Plasma LDL-cholesterol correlated directly with platelet plasma membrane cholesterol (Y=0.28X+0.16;R 2 =0.39).The average platelet plasma membrane cholesterol concentration was ~2-fold larger in T2D than in control subjects (P<0.05).Cyclic GMP production in response to exogenous NO was ~4-fold larger in controls than in T2D (P<0.05).Artificial elevation of membrane cholesterol resulted in 50 % decrease in the initial rates of NO-uptake.Elevated plasma cholesterol could be a contributing factor to T2D-induced platelet hyperactivity, since it correlated with increased plasma membrane cholesterol, the attenuation of NO-diffusion into platelets and the lowering of cGMP biosynthesis.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot 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.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 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) | 0.001 | 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 source (direct Gemma or distilled Codex), 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".