Abstract 35: Plasma Fibronectin is a Vital Supportive Factor in Hemostasis and a Unique Self-Limiting Regulator in Thrombosis
Bibliographic record
Abstract
The role of plasma fibronectin (pFn) in thrombosis/hemostasis is controversial. We previously demonstrated that pFn supports thrombosis in pFn-/- mice. Interestingly, depletion of pFn in fibrinogen (Fg)/VWF-/- mice resulted in enhanced thrombus formation, revealing a functional switch of pFn in the absence of Fg/VWF. However, the mechanism controlling this switch is unknown. Furthermore, the hemostatic function of pFn is unclear. To address these questions, we established Fg/pFn-/- and VWF/pFn-/- mice in addition to triple deficient mice (Fg/VWF/pFn-/-, TKO). TKO mice had significantly higher mortality (23.1% vs. 9.1%) and longer tail bleeding time than their pFn+ Fg/VWF-/- littermates. Autopsy revealed severe subcutaneous or abdominal bleeding. pFn depletion in Fg-/- mice also increased mortality from 5.5% to 25.6% and prolonged bleeding times; the latter effect was reversed with pFn infusion. Using intravital microscopy, we found that pFn deposition at the site of injury preceded significant platelet accumulation, suggesting that pFn is an efficient and rapid hemostatic factor. Based on thromboelastography, fibrin clots from pFn+ mice were significantly stronger than those from pFn-/- mice. Consistent with this, inferior vena cava occlusion was significantly delayed in pFn-/- mice. Under confocal microscopy, fluorescently-labeled pFn was actively recruited into the fibrin network in mouse and human plasma. Under electron microscopy, physiological levels of pFn doubled the diameter of fibrin fibers, suggesting that pFn contributes to lateral aggregation of fibrin protofibrils. Interestingly, pFn enhances platelet aggregation when linked with fibrin and inhibits aggregation when fibrin is absent. pFn therefore gradually switches from supporting hemostasis to inhibiting thrombosis and vessel occlusion following the fibrin gradient that decreases farther from the injured endothelium. Our data established pFn as an important supportive factor in hemostasis and a unique self-limiting regulator of thrombosis, suggesting the therapeutic potential of pFn transfusion in controlling bleeding complications, particularly for those receiving antithrombotic therapy for heart attack and stroke.
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) | 0.003 | 0.001 |
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".