Abstract 228: Niacin Improves Human Microvascular Endothelial Cell Angiogenic Function Under Lipotoxic and Hypoxic Conditions
Bibliographic record
Abstract
Niacin (nicotinic acid) can reduce vascular disease risk, but its mechanism of action is controversial, and may not be dependent on systemic lipid modifying effects. It has recently been shown to improve endothelial function and vascular regeneration, independent of correcting dyslipidemia, in rodent models of vascular injury and ischemia, and metabolic disease. As a potential biosynthetic precursor for NAD + , niacin could elicit vascular benefits through NAD + -dependent, sirtuin (SIRT) mediated responses. Or, it may act through its receptor, GPR109A, to promote endothelial function, though endothelial cells are not known to express this protein. We tested the hypothesis that niacin directly improves endothelial cell function under lipotoxic and low oxygen conditions, and investigated the potential mechanism(s) involved. We measured human microvascular endothelial cell (HMVEC) angiogenic function, by tube formation on Matrigel (18 h), during fatty acid overload (0.5 mM palmitate, oleate, or palmitate plus oleate) under either normoxic (20% O 2 ) or low oxygen (2% O 2 ) conditions. Both supplementation with excess palmitate and incubation at 2% O 2 inhibited tube formation compared to control conditions (-38% and -44%, respectively, n=5, p<0.05). Although niacin (10 μM) improved tube formation in the presence of excess palmitate, during both normoxia (35%, n=5, p<0.05) and hypoxia (34%, n=5, p<0.05), it did not increase [NAD + ]/[NADH] ratios or SIRT1 activity. Gene expression microarray analyses further showed that niacin did not induce expression of known SIRT1 regulated genes. However, we made the novel observation that HMVEC express GRP109A. Selective activation of the receptor with acifran recapitulated niacin induced improvements in tube formation during palmitate overload in 20% O 2 (53%, n=3, p<0.05), while GPR109A siRNA diminished the effect (16%, n=3, p<0.05). We concluded that niacin improves HMVEC angiogenic function under lipotoxic and hypoxic conditions. During normoxia, this effect appears to be independent of NAD+ synthesis and SIRT1 activation, but likely occurs through activation of GPR109A. These findings may have implications for the use of niacin in ischemic vascular disease associated with metabolic disease.
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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 | 0.000 | 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) | 0.004 | 0.001 |
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".