Angiotensin II induces sex-specific ventricular remodeling in aging C57Bl/6 mice
Bibliographic record
Abstract
Renin-angiotensin system (RAS) activation in heart failure (HF) increases circulating angiotensin II (AII). This increases blood pressure (BP) and promotes adverse ventricular remodeling that makes HF worse. Although human HF increases with age and differs between the sexes, preclinical studies have used young, mostly male animals. We investigated sex differences in AII-induced cardiac remodeling in aging C57BL/6 mice. Mice (≈16 months) were infused with AII (3 mg/kg/day; 6 weeks; osmotic minipumps). BP (tail cuff), ventricular structure/function (echocardiography), M1 (Cd80/Mcp-1/Cd68), and M2 (Mrc1) macrophage markers and profibrotic markers (transforming growth factor beta (Tgfb1), collagen 1 (Col1a1), collagen 3 (Col3a1); qPCR/Western blot) were measured. AII treatment increased BP and heart weight/tibia length in both sexes. Interestingly, AII increased wall thickness in females but reduced it and caused left ventricular (LV) dilation in males only. AII increased E/A ratios in males and isovolumic relaxation time in both sexes, indicative of diastolic dysfunction. However, isovolumic contraction time (IVCT) increased (12.0 ± 0.7 vs. 24.3 ± 3.0 ms; p = 0.0001) and ejection fraction (EF) declined in males (68.9 ± 1.9 vs. 46.1 ± 4.5; p = 0.0001), which indicates marked systolic dysfunction. By contrast, IVCT was unaffected, and EF declined but remained well above 50% in females (68.1 ± 1.3 vs. 55.9 ± 2.0; p = 0.01). mRNA for macrophage markers (Cd80, Mrc1), Tgfb1, Col1a1, and Col3a1, plus collagen 1 protein increased in treated male ventricles. By contrast, AII increased collagen 3 protein in females compared to treated males. Thus, AII promotes inflammatory/profibrotic signaling, which contributes to fibrosis and impairs systolic function in aging males. Older females appear resistant to these effects.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| 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".