Abstract 258: Progressive Diastolic Dysfunction, Perivascular Fibrosis and Left Ventricular Hypertrophy in LDL-Receptor Deficient Mice
Bibliographic record
Abstract
Background and Aim: Left ventricular diastolic dysfunction (LVDD) refers to abnormal filling of the left ventricle (LV) due to its impaired relaxation or increased stiffness. Animal models of LVDD are limited and underlying mechanisms remain largely unknown. We aimed to assess LVDD in Ldlr -/- mice using imaging and gene expression measurements. Methods: Sixty-nine Ldlr -/- mice were fed with a western-type diet supplemented with vitamin D 2 (30 U/g/day) for 20 weeks to induce LVDD. Eight normal mice were fed with a normal diet and used as control group. Serial echocardiograms were used to assess cardiac structure and function, histological analyses were done on LV sections, and RT-PCR was performed on LV samples. Results: Echocardiographic results show the development of LVDD over time (P values <0.05), with a modest increase in LV mass/BW and preserved systolic function. There was an increase of perivascular fibrosis (14.9%±1.0% (14.9 to 100) vs 9.0%±1.6%; (9 to 100), respectively, P<0.01) in Ldlr -/- mice compared to controls as detected by Masson’s trichrome staining, which was correlated with increased mRNA expression for TGFß1 and Smad2 and 3 (P<0.05 for all). This was accompanied by numerical increases in Type I and III collagen mRNAs ( Col I : 1.33 (1.03; 1.97) vs 1.03 (0.90; 1.11), P=0.06; Col III : 1.49±0.30 vs 1.00±0.10, P=0.14). The angiotensin II precursor Agt mRNA level was also higher (1.07±0.08 vs 0.72±0.05; P<0.01) in Ldlr -/- mice compared to controls. Conclusion: Taken together, Ldlr -/- mice fed with a western diet supplemented with vitamin D 2 develop progressive LVDD, perivascular fibrosis and mild left ventricular hypertrophy, which represents a new model of lipid-mediated diastolic dysfunction that may be used in future studies for the evaluation of novel treatments.
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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 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.005 | 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".