NAD <sup>+</sup> depletion and altered mitochondrial function are key to the establishment of placental dysfunction in an inflammatory-driven subclass of preeclampsia
Bibliographic record
Abstract
Abstract Preeclampsia (PE) is a pregnancy associated hypertensive disease. It is one of the major causes of pregnancy-related maternal/perinatal adverse health outcomes, with a lack of highly effective preventative strategies and/or therapeutic interventions. Our group has previously identified distinct subclasses of pathophysiology underlying a PE diagnosis, one of which exhibits heightened immune activation at the gestational parent-fetal interface, identified as inflammatory-driven PE. In non-pregnant populations, chronic inflammation is associated with reduced cellular availability of NAD + , a vitamin B3-derived metabolite involved in energy metabolism and mitochondrial function. Interestingly, specifically in placentas from women with inflammatory-driven PE, we observed increased activity of NAD + -consuming PARP enzymes and reduced NAD + content. Moreover, these placentas had decreased expression of several mitochondrial oxidative phosphorylation (OXPHOS) proteins and evidence of oxidative damage. This human data was supported by cell culture findings, which likewise demonstrated increased PARP activity, coupled to decreased mitochondrial respiration rates and decreased invasive function of cultured HTR8 human trophoblast cells, following inflammatory induction by TNF-α. Importantly, these adverse inflammatory effects were attenuated by boosting cellular NAD + levels with nicotinamide riboside (NR). Finally, using an LPS-induced rodent model of inflammatory-driven PE, we demonstrated that NR administration (200mg/kg/day) from gestational day (GD) 1-19 could prevent the development of maternal hypertension and fetal/placental growth restriction, improve placental mitochondrial function, reduce placental inflammation and oxidative stress. Thus, this study demonstrates the critical role of NAD + metabolism in maintaining healthy placental function and identifies NAD + boosting as a promising preventative strategy for the inflammatory-driven subclass of PE. One sentence summary Boosting NAD + levels prevent inflammatory-driven preeclampsia by improving placental mitochondrial function.
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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) | 0.001 | 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".