Abstract 058: Sirt3 Impairment and SOD2 Hyperacetylation Drive Vascular Oxidative Stress and Hypertension
Bibliographic record
Abstract
Aging is associated with increased incidence of hypertension and a decline of the mitochondrial energy regulator deacetylase Sirt3. A major mitochondrial antioxidant enzyme, SOD2, is inhibited by acetylation and its deacetylation by Sirt3 restores SOD2 activity. We hypothesized that loss of Sirt3 activity increases vascular oxidative stress due to SOD2 hyperacetylation and that this promotes hypertension. The combination of angiotensin II and TNFα, which is produced by inflammatory cells in hypertension, synergistically reduced Sirt3 expression, induced SOD2 acetylation and increased mitochondrial superoxide (O 2 • - ) in human aortic endothelial cells (HAEC). mitoEbselen, which scavenges mitochondrial H 2 O 2 , prevented SOD2 acetylation in HAEC and normalized mitochondrial O 2 • - suggesting redox-dependent modulation of Sirt3. In intact mice, chronic AngII infusion (490 ng/kg/min) reduced vascular Sirt3 expression by 20%, caused Sirt3 S-glutathionylation, SOD2 hyperacetylation and reduced SOD2 activity by 42%. Mice transgenic for mitochondria-targeted catalase exhibited reduced Sirt3 S-glutathionylation, no SOD2 hyperacetylation, maintenance of SOD2 activity and no increase in mitochondrial O 2 • - . The functional role of Sirt3 S-glutathionylation was further supported by mitoEbselen treatment of WT and Sirt3 -/- mice after the onset of AngII-induced hypertension. mitoEbselen reduced vascular oxidative stress and hypertension in WT but not in Sirt3 -/- mice. In Sirt3 -/- mice, low dose AngII (200 ng/kg/min) caused greater hypertension (150 mm Hg) than in WT (128 mm Hg, P<0.01) and AngII-infused Sirt3 -/- mice produced less nitric oxide that WT, as detected by electron spin resonance (70 pmol/aorta vs 110 WT+AngII, P< 0.01). We further showed that treatment with the mitochondria targeted SOD2 mimetic mitoTEMPO, initiated after the onset of AngII-induced hypertension lowered blood pressure and improved vasodilatation in both WT and Sirt3 -/- mice, further supporting a role of mitochondrial O 2 • - in hypertension. These data indicate that reduced Sirt3 activity occurs in hypertension due to S-glutathionylation and that this leads to SOD2 hyperacetylation and inactivation, promoting vascular oxidative stress and blood pressure elevation.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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) | 0.001 | 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) | 0.006 | 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".