Abstract 5669: Monocytic Cells Are Required for Endothelial Regeneration
Bibliographic record
Abstract
Background: Circulating endothelial progenitor cells (EPC) contribute to endothelial cell (EC) regeneration and are predictors for cardiovascular events. Systemic treatment with EPC fosters the repair of damaged endothelium. We have shown that transfusion of mononuclear cells (MNC) lead to an even more pronounced regeneration of the endothelium compared to EPC transfusion. Here, we determine the role of monocytic CD11b+ cells in EC regeneration. Methods/Results Re-endothelialization, neointima formation, and endothelial function was determined in wild-type (WT) mice treated with intravenous injections of spleen-derived MNC, CD11b-depleted MNC, CD11b+ cells, or cell-free vehicle after EC denudation. EC regeneration was enhanced and neointima formation reduced after transfusion of total MNC and CD11b+ cells but not after CD11b-depleted cells. We further determined the role of monocytes in a model of a disseminated EC damage. In ApoE−/− mice, transfusion of CD11b+ cells and total MNC but not CD11b-depleted MNCs improved endothelial function. To determine the role of endogenous monocytes on EC repair, mice were treated with clodronate-liposomes (10 μ l/g bw) to deplete monocytes. Re-endothelialization after focal EC denudation was significantly diminished in clodronate-treated compared to vehicle-treated mice. Next, we selectively depleted CD11b+ monocytes and tissue-residual macrophages using CD11b-DTR transgenic mice. Treatment with diphtheria toxin (DT) results in the complete ablation of circulating monocytes/tissue-resident macrophages. DT treatment was performed for 10 days (15ng/g bw). At day 5 post EC damage, the denuded area was significantly larger in DT treated compared to vehicle treated mice. Transfusion of Sca1+ cells significantly enhanced re-endothelialization in vehicle-treated CD11b-DTR mice but not in DT treated mice. Finally, transfusion of CD11b+ cells in CD11b-DTR mice treated with either vehicle or DT resulted in a comparable enhancement of re-endothelialization. Conclusion Here we demonstrate that circulating CD11b+ monocytes contribute to EC regeneration. Depletion of circulating monocytes is associated with a delay in re-endothelialization after EC damage and is not rescued by Sca1+ cells.
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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) | 0.000 | 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 | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.006 | 0.003 |
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".