Oxidized Low-density Lipoprotein Inhibits Endothelium-dependent Vasodilation by an Antioxidant-sensitive, Lysophosphatidylcholine-independent Mechanism
Bibliographic record
Abstract
Previous studies have shown that oxidized low-density lipoprotein (LDL) can impair endothelial function and that this can be overcome in vivo by administration of vitamin E. However, it is unclear whether this effect of oxidized LDL is due to lysophosphatidylcholine or other components of oxidized LDL, and it is also uncertain if the protective effect of vitamin E is related to its antioxidant action. The objectives of the current study were to define how much of the effect of extensively oxidized LDL on endothelium-dependent relaxation (EDR) was in fact due to lysophosphatidylcholine, to determine if the effect of oxidized LDL involved oxidant stress to the endothelium, and, if so, to ascertain if this could be blocked by oxyradical scavengers or antioxidants. Endothelial function was assessed by measuring vasodilation in preconstricted rat mesenteric artery rings in response to acetylcholine. In the presence of 100 microg/mL oxidized LDL, 25-fold higher concentrations of acetylcholine were required for the same degree of vasorelaxation. Similar concentrations of native LDL or acetyl LDL had no effect, but 100 microg/mL phospholipase A(2)-treated LDL or 20 microM lysophosphatidylcholine produced a similar inhibition of EDR. Removal of more than 90% of lysophosphatidylcholine from oxidized LDL did not affect its ability to inhibit EDR, nor did treatment of oxidized LDL with borohydride. This effect of oxidized LDL was blocked by preincubation of arterial rings with vitamin E, probucol, or BO-653 (a potent lipophilic antioxidant), but not by superoxide dismutase. In contrast, the inhibition of EDR by lysophosphatidylcholine was unaffected by antioxidants. Calphostin C prevented the inhibition of EDR by oxidized LDL and lysophosphatidylcholine. These studies demonstrate that at least part of the effect of oxidized LDL on EDR is independent of lysophosphatidylcholine, lipid peroxides, and superoxide release but appears to involve intracellular oxidative stress and protein kinase C activation.
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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 | 0.003 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.001 |
| 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".