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Record W6990663147

The Effect of Cardiolipin on Vascular Smooth Muscle Cell
\nDedifferentiation, Function, and Mitochondrial Respiration

2017· dissertation· en· W6990663147 on OpenAlexfundno aff

Bibliographic record

VenueSpectrum Research Repository (Concordia University) · 2017
Typedissertation
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicCalpain Protease Function and Regulation
Canadian institutionsnot available
FundersCanadian Institutes of Health ResearchConcordia University
KeywordsCardiac muscleContractilityCardiolipinSkeletal muscleMyoglobinuria
DOInot available

Abstract

fetched live from OpenAlex

The initial phases of atherosclerosis involve the transition of normal vascular smooth muscle cells (VSMCs) to a synthetic, dedifferentiated phenotype, which can migrate and proliferate. This could potentially obstruct blood flow, which, when destined to the cardiomyocytes, can lead to myocardial infarction. Studies have demonstrated that cardiomyocytes, undergoing apoptosis, release a phospholipid molecule called cardiolipin (CL) into the systemic circulation. The objective of this project was to investigate the impact of cardiolipin on VSMCs, specifically addressing cellular dedifferentiation, migration, proliferation, and whether these modifications are mitochondria-mediated. The effect of CL on aortic contractility was also examined. Using adult mice aortas, we quantified a number of differentiation and dedifferentiation markers (αsmooth actin, calponin1, calpain I, and MMP14), following 48 hours of organ culture with physiological concentrations of CL (1µM and 10 µM) through immunoblotting. These CL concentrations were also used to investigate VSMC migration and proliferation over six days using cell culture, and to study blood vessel contraction following 48 hours of organ culture. Additionally, the acute effects of cardiolipin on VSMC mitochondria were examined through the use of high-resolution respirometry and selected substrate-inhibitor-uncoupler titration protocols. We found that calponin1 protein expression has significantly decreased by CL, while the other proteins remained unaffected. VSMC migration was ceased when treated with CL, while proliferation and contraction seemed unaffected. Mitochondrial respiration was significantly decreased for complex I and III. In conclusion, our results demonstrate that CL significantly reduces VSMC migration, calponin levels, and mitochondrial respiration, which could potentially act as an anti-atherosclerotic factor.

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 distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesScience and technology studies
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.627
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0010.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

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.

Opus teacher head0.008
GPT teacher head0.240
Teacher spread0.232 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

Study designBench or experimental
Domainnot available
GenreEmpirical

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".

Quick stats

Citations0
Published2017
Admission routes1
Has abstractyes

Explore more

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