Role of microprojections in myoendothelial feedback – a theoretical study
Bibliographic record
Abstract
Key points Endothelial microprojections (MPs) are cellular extensions of endothelial cells (ECs) that may be involved in regulation of smooth muscle cell (SMC) constriction in blood vessels. We developed computational models to investigate the role of MPs in generating EC feedback during SMC stimulation. The models account for the geometry of MPs and heterogeneous distribution of membrane channels and receptors in an EC. Simulations show that SMC stimulation causes calcium release in and around EC MPs that activates hyperpolarizing currents in ECs and moderates SMC constriction. The results help us better understand the mechanisms that regulate blood flow and pressure. Abstract We investigated the role of myoendothelial projections (MPs) in endothelial cell (EC) feedback response to smooth muscle cell (SMC) stimulation using mathematical modelling. A previously developed compartmental EC–SMC model is modified to include MPs as subcellular compartments in the EC. The model is further extended into a 2D continuum model using a finite element method (FEM) approach and electron microscopy images to account for MP geometry. The EC and SMC are coupled via non‐selective myoendothelial gap junctions (MEGJs) which are located on MPs and allow exchange of Ca2+, K+, Na+ and Cl− ions and inositol 1,4,5‐triphosphate (IP3). Models take into consideration recent evidence for co‐localization of intermediate‐conductance calcium‐activated potassium channels (IKCa) and IP3 receptors (IP3Rs) in the MPs. SMC stimulation causes an IP3‐mediated Ca2+ transient in the MPs with limited global spread in the bulk EC. A hyperpolarizing feedback generated by the localized IKCa channels is transmitted to the SMC via MEGJs. MEGJ resistance (Rgj) and the density of IKCa and IP3R in the projection influence the extent of EC response to SMC stimulation. The predicted Ca2+ transients depend also on the volume and geometry of the MP. We conclude that in the myoendothelial feedback response to SMC stimulation, MPs are required to amplify the SMC initiated signal. Simulations suggest that the signal is mediated by IP3 rather than Ca2+ diffusion and that a localized rather than a global EC Ca2+ mobilization is more likely following SMC stimulation.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.001 |
| Insufficient payload (model declined to judge) | 0.005 | 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".