Abstract P3043: Functional Role Of Endothelial Mitochondrial Oxidative Stress In Cognitive Impairment: Effects Of L-arginine In Hypertensive Frail Older Adults
Bibliographic record
Abstract
Background: Hypertension is common in older adults, particularly in frailty. The association of hypertension and frailty leads to a high-risk of cognitive impairment in older adults. Endothelial dysfunction has been shown to underlie both hypertension and cognitive impairment. L-Arginine is an amino acid involved in many biological processes and is a substrate of two enzymes: nitric oxide (NO) synthase (NOS) and arginase (NOA). L-Arginine is fundamental for NO production by endothelial cells, regulating vascular tone and cardiovascular homeostasis, improving inflammation and oxidative stress. On these grounds, we hypothesized that L-Arginine could improve cognitive impairment via its effect on endothelial mitochondria. Methods: To assess the effects of L-Arginine on endothelial oxidative stress and cognitive function, we used an in vitro and a clinical approach. First, we treated with L-Arginine human umbilical vein endothelial cells (HUVECs). HUVECs were cultured in EGM-2 medium and incubated at 37°C and 5% CO 2 . HUVECs were plated on glass bottom culture dishes and treated with Angiotensin II (1 μM) and Angiotensin II with L-Arginine (500 μM) in EGM-2 medium for 24h. The generation of reactive oxygen species (ROS) was quantified using MitoSOX™ Red (an established ROS probe that accumulates in mitochondria), incubating cells for 10 min at 37°C and 5% CO 2 , as we previously described. We then designed a single-blind, placebo-controlled, parallel-group, randomized trial to observe the effects of 4-weeks oral supplementation of L-Arginine on global cognitive function of hypertensive frail older patients. Results: In vitro , we demonstrated that L-Arginine significantly attenuated Angiotensin II-induced oxidative stress in endothelial cells. Co-treatment of HUVECs with Ang II and L-Arginine significantly attenuated mitochondrial ROS production (p<0.001). In the clinical study, we evaluated 35 frail hypertensive elderly patients assigned to L-Arginine and 37 assigned to placebo: at follow-up, we found a significantly improved Montreal Cognitive Assessment (MoCA) test score in the L-Arginine treated arm compared to placebo (p<0.05). Conclusions: Taken together, our findings indicate for the first time that oral L-Arginine supplementation improves cognitive impairment in frail hypertensive older adults through a mechanism that involves endothelial mitochondrial ROS.
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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 | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".