A Genetic Locus Accentuates the Effect of Volume Overload on Adverse Left Ventricular Remodeling in Male and Female Rats
Bibliographic record
Abstract
Although increased left ventricular (LV) mass is highly predictive of cardiovascular morbidity and mortality in humans, it has never been verified in an experimental model that naturally occurring alleles linked to increased LV mass under basal conditions also associate with worsened cardiovascular prognosis. Because we have shown previously that locus Cm24 on chromosome 5 was responsible for differences in LV mass between WKY and WKHA rats, we used WKY.WKHA-(D5Rat45-D5Rat245) congenic rats (where locus Cm24 has been transferred from WKHA into WKY rats) to test how naturally occurring gene variants present in Cm24 would, in addition to their effects under basal conditions, affect LV mass remodeling and/or function in the context of overload. Volume overload was induced in WKY, WKHA, and WKY.WKHA congenic rats by surgical creation of an aorto-caval fistula. In females, the fistula had no effect on the hearts of WKY rats, yet it induced dilated eccentric hypertrophy and isolated diastolic dysfunction in WKHA and WKY.WKHA congenic rats, along with signs of congestive heart failure. In males, the surgical maneuver induced only mild or inconsistent responses in WKY rats but had much more pronounced effects in WKHA and WKY.WKHA congenic rats. Altogether, our data show that a genetic locus that induces, under basal conditions, either mild or no concentric LV remodeling in either male or female rats, respectively, associates with LV dilatation and dysfunction in both sexes when the hearts are additionally challenged.
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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) | 0.001 | 0.000 |
| Bibliometrics | 0.002 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
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".