The Role of the Axonal Guidance Cue Semaphorin 3A in Innervation of the Postnatal Heart in Health and Disease
Bibliographic record
Abstract
During cardiac development, the heart is innervated by the autonomous nervous system. After development, neurons of the autonomic nervous system have limited capacity for growth and regeneration. However, in recent decades, it has become clear that cardiac nerves can regenerate after cardiac damage. Excessive reinnervation, so-called sympathetic hyperinnervation, may render patients vulnerable to ventricular arrhythmias and heart failure. Several studies have investigated axonal guidance cues as mediators of cardiac innervation. Axonal guidance cues direct neuronal growth of the axon and play a significant role in the regeneration and remodelling of cardiac autonomic innervation after cardiac damage. This review focusses on the current literature regarding the axonal guidance cue group of semaphorins and their function in the healthy and diseased postnatal heart. In view of cardiac innervation, most studies have focussed on semaphorin 3A (SEMA3A), whereas less is known about the function of the other semaphorin classes. SEMA3A is a neuronal repellent and is associated with a decrease in the density of sympathetic neurons in the heart. Its decline in expression after myocardial infarction plays a role in the development of sympathetic hyperinnervation and the subsequent increased risk of ventricular arrhythmias. In congestive heart failure, the opposite occurs: an increase in SEMA3A expression underlies decreased nerve density that may also serve as a substrate for ventricular arrhythmias. Although the literature on their role in cardiac innervation is still relatively scarce, semaphorins, especially SEMA3A, seem worthwhile to consider when exploring options to modulate pathologic innervation patterns in cardiovascular disease.
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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 | 0.001 | 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 | 0.001 |
| 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".