Abstract 4370032: Cardiac and renal expression of angiotensin II type 1 receptor and its association with fibrosis and heart function in ischemic heart failure rat models
Bibliographic record
Abstract
Introduction: Despite the growing interest in the role of Angiotensin II type 1 receptor (AT 1 R) in left ventricular remodeling and heart failure, little is known about its association with heart function and fibrosis. This study evaluated temporal changes in myocardial and renal AT 1 R expression in ischemic heart failure rat models, and evaluated its potential as an early diagnostic marker for heart failure. Hypothesis: Upregulation of cardiac and renal AT 1 Rs occurs during early ventricular remodeling, prior to a reduction in left ventricular function as measured by echocardiography. Methods: Male Sprague-Dawley rats (n=55, 200-250g) were randomized and subjected to the following surgeries: Sham, Ischemia/Reperfusion (I/R, 20 min ligation) and Permanent Ligation (PL) of the left anterior descending artery. Heart function was assessed by weekly echocardiography for 12 weeks. AT 1 R expression and fibrosis levels in the heart (infarct and remote areas) and kidneys (cortex and medulla) were assessed at 2 hours, 1 and 3 days; 1, 3, 5, 7 and 12 weeks post-surgery using in vitro 125 I-[Sar 1 , Ile 8 ]-Angiotensin II autoradiography and picrosirius red staining, respectively. One-Way ANOVA, t-test and Pearson’s correlation tests were used for the association of AT 1 R, fibrosis and heart function. Results: Left ventricular ejection fraction was reduced by 19% (p<0.01) at 2 hours and 35% (p<0.0001) by week-7 in PL animals, while remaining unchanged in I/R. Compared to Shams, the highest increase (p<0.0001) in cardiac fibrosis in the infarcted area was observed at day-3 (+10,055%) in I/R and at day-1 (+17,850%) in PL. In Shams, renal cortex and medulla exhibited 50-fold higher (p<0.0001) AT 1 R levels compared to the heart. The highest increase (p<0.0001) in cardiac AT 1 R levels in I/R was at week-1 (+1,386%) and at day-3 (+1,100%) in PL. Infarct areas consistently had higher AT 1 R levels and fibrosis than remote areas. Renal AT 1 R expression and fibrosis remained unchanged across all groups. Cardiac AT 1 R levels strongly correlated with fibrosis in I/R (r=0.756, p<0.0001) and with LVEF in PL (r=-0.722, p<0.05). Conclusions: Cardiac AT 1 R expression reflects early cardiac remodeling and fibrosis in I/R animal models and may potentially be a more sensitive marker for detecting and studying at a molecular level cardiac remodeling than echocardiographic parameters. Unchanged renal AT 1 R expression indicates limited sensitivity of renal AT 1 R as a marker for heart failure detection.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 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".