Abstract P176: Pharmacological Inhibition Of Drp1 Dependent Mitochondrial Fission Alleviates Mitochondrial Dysfunction-associated Cell Death In Vascular Smooth Muscle Cells
Bibliographic record
Abstract
Background: Vascular smooth muscle cell (VSMC) death has been linked to the pathogenesis of various vascular diseases. Excessive mitochondrial fission in response to pathological stimuli contributes to apoptosis, thus inhibition of mitochondrial fission appears to be a promising therapeutic target in vascular disease. Mitochondrial division inhibitor 1 (mDivi-1) inhibits Drp1 dependent fission by attenuation of its GTPase activity. The limited literature on mDivi-1-mediated attenuation of VSMCs apoptosis and its effect on the pathogenesis of vascular disease warrants further investigation. Methods and Results: Staurosporine (STS)-induced apoptosis and attenuated cell proliferation were observed in VSMCs. The treatment with mDivi-1 ameliorated these detrimental effects of STS and led to reduced apoptosis, and increased cell proliferation. The mitochondrial fission was evaluated using Mitotracker Red staining which showed reduced mitochondrial fragmentation with significantly higher mitochondrial networks, mean branch length, and mitochondrial footprint upon treatment with mDivi-1. Drp1 levels were increased in STS-treated cells with localization in the mitochondria. Cellular and mitochondrial stress response assessed by DHE and mitosox staining. mDivi-1 treatment attenuated STS-induced ROS generation in VSMCs. Mitochondrial function via evaluation of Mitochondrial permeability transition pore (mPTP) opening, mitochondrial membrane potential, and bioenergetic profile showed significantly reduced mPTP opening and higher metabolic potential represented by OCR and ECAR in mDivi-1-treated cells compared to STS group. The autophagy marker LAMP1 showed increased colocalization in mitochondria of STS-treated VSMCs. The apoptotic proteins were assessed using a protein array. The mDivi-1 treated VSMCs showed significantly reduced autophagy and apoptosis-related proteins. This suggested attenuation of apoptosis-mediated mitochondrial damage upon treatment with mDivi-1. Conclusion: Pharmacological inhibition of mitochondrial fission provides a potential therapeutic target in VSMCs death-associated vascular diseases.
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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 | 0.000 |
| 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 | 0.002 |
| Insufficient payload (model declined to judge) | 0.013 | 0.002 |
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".