Pharmacological inhibition of mitochondrial fission mitigates experimental thoracic aortic aneurysm
Bibliographic record
Abstract
Abstract Thoracic aortic aneurysm (TAA) is increasingly recognized as a vascular degenerative disease and is typically diagnosed incidentally due to its asymptomatic nature. TAA is clinically associated with the dilation of the aorta and excessive vascular remodeling, which can lead to aortic rupture if left untreated. Angiotensin II (Ang II), an active peptide in the renin-angiotensin system, has been widely implicated in the development of TAA. The current study investigated the role of mitochondrial dynamics in the onset and progression of TAA. Male ApoEKO mice (8-10 weeks old) were infused with Ang II (1.44 mg/kg/day) and treated with mitochondrial division inhibitor 1 (mdivi-1) at a dose of 0.12 mg/kg/day. After 4 weeks of Ang II infusion, the ApoEKO mice developed TAA. Excessive mitochondrial fission was observed in thoracic vascular smooth muscle cells (vSMCs) using transmission electron microscopy (TEM) and confocal microscopy in response to angiotensin II (Ang II) treatment, which was reduced by mdivi-1. Echocardiographic and histological analyses of the Ang II-infused thoracic aorta revealed increased aortic dilation, vascular remodeling, and perivascular fibrosis. Pathological changes associated with Ang II-induced TAA were mitigated by mdivi-1. Co-treatment of isolated adult murine thoracic aortic vSMCs with mdivi-1 resulted in decreased mitochondrial fission, hyperproliferation, and phenotypic switching, accompanied by improved mitochondrial metabolism. Treatment with mdivi-1 inhibited Ang II-induced NF-κB signaling in vSMCs by blocking the nuclear translocation of p65 and cell cycle markers, thereby limiting inflammation and hyperproliferation. In conclusion, the inhibition of mitochondrial fission reduced pathological changes by mitigating vascular remodeling, vSMC hyperproliferation, and vSMC phenotypic switching associated with Ang II-induced TAA. The clinical utility of inhibiting mitochondrial fission warrants further investigation, which may lead to a novel therapeutic strategy for preventing TAA development.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.002 | 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".