Breakdown of the Apical Spectrin Network Leads to Endothelial Dysfunction and Vascular Stiffening in Pulmonary Arterial Hypertension
Bibliographic record
Abstract
Recently, a critical role for a spectrin cytoskeletal network in sensing of shear and regulation of vascular stiffness has been described in systemic endothelial cells. The loss of spectrin resulted in the disappearance of apical caveolae, dysregulated eNOS activation, and a lack of calcium response to shear. Since spectrin can be broken down in vivo by calpain, which is activated in pulmonary arterial hypertension, I hypothesized that spectrin breakdown may represent a key mechanism underlying endothelial dysfunction.I report an increased prevalence of spectrin digesting proteases and spectrin breakdown products in the lungs of monocrotaline treated rats, along with decreased levels of caveolin-1 and a reduction in apical caveolae, a trend that was reversed by administration of calpeptin, a calpain inhibitor. Calpeptin was also shown to be protective against severe pulmonary hypertension in MCT rats. Furthermore, I determined that the knockdown of spectrin in endothelial cells results in internalization of caveolin-1 and impaired endothelial responses to shear. My studies detail a critical role for the spectrin cytoskeleton in the development of endothelial dysfunction and highlight the therapeutic potential of preventing its breakdown via calpain inhibition.
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 | 0.001 |
| 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".