The Effects of Cardiolipin on Vascular Smooth Muscle Cell Dedifferentiation and Migration
Bibliographic record
Abstract
PURPOSE The initial phases of atherosclerosis involve the transition of smooth muscle cells (SMCs) to a synthetic, dedifferentiated phenotype, which is associated with alterations in receptor, ion channel and contractile filament composition. The late, irreversible atherosclerosis stages are characterized by SMC migration and subsequent formation of a ‘neointima.’ This leads to blood flow obstruction which, when destined to the cardiomyocytes, induces hypoxic conditions and myocardial infarction. Apoptotic cardiomyocytes release a phospholipid called cardiolipin (CL) into the systemic circulation. Previously, we have shown that physiological concentrations of CL inhibit endothelial cell migration. The objective of this project was to investigate the impact of CL on SMCs, specifically addressing cellular dedifferentiation and migration . METHODS For this study, we used adult, male C57Bl/6 mice. Aortas from these mice were extracted and incubated in Dulbecco's modification of Eagle medium containing physiological CL concentrations (1 μM and 10 μM) at 37°C for 48 hours. We subsequently quantified contractile proteins (such as smooth muscle α‐actin and calponin) using immunoblotting to determine whether CL affects SMC dedifferentiation. These concentrations were also used to investigate the migration of SMCs using a migration assay. For this, we mimicked wounds by scraping off the cell culture plates' diameters to create cell‐free gaps. The plates were then incubated at 37°C for six days, during which the width of the gaps was measured every 48 hours under a light microscope. RESULTS The immunoblotting results demonstrated a significant drop in calponin in a dose‐dependent manner with increasing CL concentrations, while the other de/differentiation markers remained unchanged. The migration assay revealed that the gap width was significantly narrower in control plates compared to CL‐treated plates. CONCLUSIONS Our results suggest that the effect of physiological concentrations of CL on SMCs is calponin‐specific and does not initiate dedifferentiation within 48 hours. The significantly wider gaps observed in the CL‐treated plates compared to the control plates indicate the potent effect CL has on inhibiting SMC migration. Since SMC migration is considered the key step in the atherogenic progression, our migration assay data suggest that, in a physiological context, CL has the potential to arrest the progression of the disease into its irreversible stages. Thus, we hypothesize the potential involvement of CL in developing anti‐atherosclerosis therapeutics. Support or Funding Information Canadian Institute of Health Research (CIHR) This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .
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) | 0.000 | 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) | 0.001 | 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".