Abstract 10884: B-Cell-Mediated Sodium and Water Retention Contributes to Heart Failure Pathogenesis
Bibliographic record
Abstract
Background: B-cells have been shown to serve pathogenic roles in heart failure through cardiac-specific monocyte mobilization and autoantibody deposition. Beyond this, we recently showed that mice with hypomorphic c-Myb activity ( c-myb h/h ) have reduced B-cells and that B-cell deficiency is associated with increased sodium- and water-excretion and reduced blood pressure. Here, we determine the relevance of these responses in an experimental model of heart failure. Methods & Results: C57BL/6J wild-type (WT) and B-cell deficient c-myb h/h mice (male and female; aged 10-12 weeks) underwent either: (i) permanent LAD ligation to induce myocardial infarction (MI); or (ii) sham surgery. Echocardiography showed that B-cell deficiency preserved ejection fraction (53±2 vs. 44±2 %; N=6-7/group; P<0.01) and limited pathologic remodeling with reduced LVID (end-diastolic: 4.9±0.1 vs. 5.5±0.1 mm; N=6-7/group; P<0.01; end-systolic: 3.8±0.2 vs. 4.5±0.1 mm; N=6-7/group; P<0.001) at 4-weeks post-MI compared to WT. Heart weight/tibia length and right lung weight/tibia length ratios (g/mm; P<0.01), as well as pleural effusion volumes (μl; P<0.05) were increased post-MI in WT, rather than c-myb h/h mice. Indeed, mice with B-cell deficiency manifest reduced right lung weight/tibia length ratio (0.005±0.000 vs. 0.009±0.001 g/mm; N=5-6/group; P<0.01) and pleural effusion volume (17±6 vs. 55±18 μl; N=6-7/group; P<0.06) post-MI compared to WT. Underlying this decongestion, metabolic cage studies revealed that B-cell deficient mice had sustained increases in 24-h urine volume/body weight and 24-h sodium excretion/body weight ratios, which correlated with ejection fraction 4-weeks post-MI (r=0.53; N=13 pairs; P<0.05; and r=0.50; N=13 pairs; P<0.05, respectively). Conclusion: Together, these data show that B-cells play a role in sodium- and water-retention, and consequently, extracellular fluid volume expansion and congestion post-MI, and suggest that B-cells may represent a therapeutic target in heart failure.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| 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) | 0.000 | 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 teacher head, 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".