Abstract 523: Phenotypic And Metabolic Switching Of Fibroblasts In Aortic Aneurysm
Bibliographic record
Abstract
Background: Aortic aneurysm (AA) is a deadly cardiovascular disease that carries a tremendous burden worldwide. There are currently no approved pharmacological treatments to prevent or stop the progression of AA. Fibroblasts occupy the tunica adventitia layer of blood vessels and, during stress and in many cardiovascular diseases, fibroblasts become activated into myofibroblasts. Metabolic and mitochondrial abnormalities have also been observed in fibroblasts during various other cardiovascular diseases. The aim of this project is to assess the phenotypic and metabolic state of fibroblasts in aortic aneurysm using in vitro and in vivo murine models. Methods and Results: Aortic adventitial fibroblasts isolated from wild-type mice were used for all in vitro experiments. Angiotensin II (Ang II) was used as an in vitro inducer of fibroblast activation. Preliminary investigations suggest mitochondrial abnormalities in activated fibroblasts that ensued after in vitro Ang II treatment. Alpha smooth-muscle actin, a myofibroblast marker, was upregulated in fibroblasts following Ang II treatment. Activation of fibroblasts in response to Ang II was also associated with activation of Drp1, an inducer of mitochondrial fission. Using Seahorse extracellular flux analysis and Mitotracker Red staining, we identified alterations in mitochondrial structural and function in response to Ang II. 8-10-week-old apolipoprotein E knockout mice, implanted with micro-osmotic pumps to infuse Ang II for 4 weeks, were used to investigate the role of Drp1 in the onset and progression of AA. A subgroup of these mice received daily injections of mdivi-1. Preliminary results validate the successful generation of a murine model of TAA suitable for investigations using a pharmacological blocker of Drp1 activity. Echocardiographic assessment of aortic structure (diameter) and function (expansion index) validated the occurrence of TAA in angiotensin II-infused ApoEKO mice, which was found to be reduced in response to mdivi-1, an inhibitor of Drp1 activity, treatment. Conclusion: The results from this study could provide novel insight into the role of mitochondrial dynamics and metabolism in contributing to AA pathophysiology.
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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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 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".