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Abstract 10884: B-Cell-Mediated Sodium and Water Retention Contributes to Heart Failure Pathogenesis
- Source :
- Circulation (Ovid); November 2021, Vol. 144 Issue: Supplement 1 pA10884-A10884, 1p
- Publication Year :
- 2021
-
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-mybh/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-mybh/hmice (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-mybh/hmice. 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.
Details
- Language :
- English
- ISSN :
- 00097322 and 15244539
- Volume :
- 144
- Issue :
- Supplement 1
- Database :
- Supplemental Index
- Journal :
- Circulation (Ovid)
- Publication Type :
- Periodical
- Accession number :
- ejs59733664
- Full Text :
- https://doi.org/10.1161/circ.144.suppl_1.10884