Lung endothelial dysfunction in heart failure: Role of impaired Ca2+ signaling and cytoskeletal reorganization
Bibliographic record
Abstract
Congestive heart failure (CHF) causes lung endothelial (EC) dysfunction, which in turn aggravates lung vascular remodeling and right ventricular failure. Here, we elucidated the mechanisms underlying lung EC dysfunction in a rat model of CHF induced by supracoronary aortic banding. Lung EC dysfunction was evident in CHF as impaired EC‐dependent vasodilation and NO synthesis in response to mechanical stress, acetylcholine or histamine, although expression of endothelial NO synthase was unmitigated. Reconstitution of cytosolic Ca 2+ ([Ca 2+ ] i ) signaling by Ca 2+ ionophore restored NO production. Impaired lung EC [Ca 2+ ] i homeostasis and signaling in CHF in response to mechanical stress, histamine, acetylcholine or thapsigargin was confirmed by real‐time fluorescence imaging, yet was not attributable to downregulation of EC Ca 2+ influx channels. Rather, we identified a massive remodeling of the endothelial cytoskeleton by increased β‐actin expression and F‐actin formation, which contributed critically to endothelial dysfunction in CHF, since cytoskeletal disruption by cytochalasin reconstituted endothelial [Ca 2+ ] i signaling and NO production. Our findings show that lung EC dysfunction in CHF results from impaired EC [Ca 2+ ] i signaling, and identify the endothelial cytoskeleton as critical regulator of EC [Ca 2+ ] i homeostasis. Sponsored by EU IP Pulmotension and Kaiserin‐Friedrich Foundation Berlin.
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".