Abstract P149: Mozobil Increases Myocardial Fibrosis via the Recruitment of Fibrocytes in the Angiotensin II--Treated Heart
Bibliographic record
Abstract
Background: Fibroblast progenitor cells (fibrocytes) are important to the development of myocardial fibrosis and suggested to migrate to the chemokine CXCL12. CXCL12 has one primary receptor, CXCR4, to which the inhibitor Mozobil competitively binds. Mozobil has been shown to inhibit recruitment of fibrocytes to the lungs following bleomycin injury, but its affects on progenitor cells in the heart remains unclear. We hypothesized that if CXCL12 is necessary for fibrocyte recruitment, Mozobil would inhibit fibrocyte infiltration into the myocardium and consequently, decrease fibrosis. Methods: C57/Bl6 mice were treated with saline (control), AngII, or AngII+Mozobil via osmotic mini-pump. Mice were sacrificed at day 3 and tissues were collected for RNA, protein and histology. Heart sections were stained with H&E and Sirius Red and analyzed for cellular infiltrate and collagen deposition, respectively. Infiltrate was measured using standardized grid counts on a single heart section. The percent area affected was the number of grids containing cellular infiltrate over the total grids containing heart tissue (∼375 grids per section). Fibrocytes were cultured from mouse peripheral blood following mobilization with Mozobil. Fibrocytes were stained for collagen-1, CD133 and CXCR4. Results: Cultured fibrocytes were positive for markers CD133 and collagen-1, as well as CXCR4. AngII infusion resulted in significant cellular infiltration, affecting 30.0 ± 4.0% (n=8) of the myocardium, relative to saline (0.3% ± 0.4; n=8). In contrast, animals receiving AngII+Mozobil had 78.9±3.1% (n=5) of the myocardium affected (p<0.05). Increased infiltrate was also associated with significantly increased collagen deposition: Control (4.3% ± 0.1), AngII (11.9% ± 1.9), and AngII+Mozobil (29.0% ± 4.8). Furthermore, the infiltrate was positive for the progenitor marker CD133. Conclusion: Our findings confirm isolated fibrocytes express CXCR4. Unexpectedly however, our findings suggest CXCL12 is not required for the migration of fibrocytes to the myocardium, based on the failure of CXCR4 blockade to limit migration. Our findings suggest that increased migration into the heart may be through the increased mobilization of progenitor cells from the bone marrow.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.008 | 0.002 |
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".