What mediates the effects of thrombospondin-1 in pulmonary hypertension? New evidence for a dual-pronged role of CD47
Bibliographic record
Abstract
This editorial refers to ‘TSP1–CD47 signalling is upregulated in clinical pulmonary hypertension and contributes to pulmonary arterial vasculopathy and dysfunction’ by Natasha M. Rogers et al. pp. 15–29. Of late, thrombospondin-1 (TSP1) has emerged as an important new mediator in pulmonary hypertension (PH), a chronic and ultimately fatal disease of the pulmonary circulation that is characterized by increased pulmonary artery pressure (>25 mmHg), and the subsequent development of right ventricular hypertrophy and ultimately, right ventricular failure. Despite the introduction of several lines of pharmacological therapies since the 1980s, 5-year mortality rates remain high,1 stressing a large unmet need for new and better therapeutic targets, and hence, a better in-depth understanding of the cellular mechanisms and signalling cascades that underlie the characteristic pathophysiology of PH. At the cellular level, PH is characterized by a simultaneous imbalance of proliferative, hypertrophic, and apoptotic processes in lung vascular endothelial and smooth muscle cells, resulting in complex and at times seemingly opposing effects that include features of both angiogenesis and vessel pruning, and thickening of the vascular intima and media with smooth muscle cells taking on both synthetic, proliferative and contractile, hypertrophic phenotypes. In addition, inflammatory and auto-immune processes as well as activation of components of the coagulation cascade contribute to the initiation and progression of PH, although their interplay with the cellular processes driving lung vascular remodelling is poorly understood. TSP1 is a multifunctional protein that is expressed and secreted from various different cell types many of which are directly or indirectly involved in the pathogenesis of PH, such as pulmonary fibroblasts, endothelial, and smooth muscle cells, as well as macrophages and platelets.2 In a recent prospective trial, circulating TSP1 levels were found to be >10 times higher in 93 patients with precapillary PH when compared with 19 control subjects without PH.3 Notably, …
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot 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.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.004 | 0.006 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.002 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".