Chronic exercise training prevents coronary artery stiffening in aortic-banded miniswine: role of perivascular adipose-derived advanced glycation end products
Bibliographic record
Abstract
Heart failure (HF) is associated with increased large conduit artery stiffness and afterload resulting in stiffening of the coronary arteries. Perivascular adipose tissue (PVAT) and advanced glycation end products (AGE) both promote arterial stiffness, yet the mechanisms by which coronary PVAT promotes arterial stiffness and the efficacy of exercise to prevent coronary stiffness are unknown. We hypothesized that both chronic continuous and interval exercise training would prevent coronary PVAT-mediated AGE secretion and arterial stiffness. Yucatan miniature swine were divided into four groups: control-sedentary (CON), aortic banded sedentary-heart failure (HF), aortic banded HF-continuous exercise trained (HF+CONT), and aortic banded HF-interval exercise trained (HF+IT). The left circumflex and right coronary arteries underwent ex vivo mechanical testing, and arterial AGE, elastin, and collagen were assessed. Coronary elastin elastic modulus (EEM) and elastin protein were lower and AGE was increased with HF compared with CON, which was prevented by both HF+CONT and HF+IT. Mouse aortic segments treated with swine coronary PVAT conditioned medium had lower EEM and elastin content and greater AGE secretion and arterial AGE accumulation in HF compared with CON, which was prevented by both HF+CONT and HF+IT. Aminoguanidine (AMG), an AGE inhibitor, prevented the reduction in EEM, arterial elastin content, and AGE accumulation in mouse aortic segments treated with PVAT conditioned medium in the HF group. Our data demonstrate efficacy for chronic continuous and interval exercise to prevent coronary artery stiffness via inhibition of PVAT-derived AGE secretion in a preclinical miniswine model of pressure overload-induced HF. NEW & NOTEWORTHY Our findings show that chronic continuous and interval exercise training regimens prevent coronary artery stiffness associated with inhibition of perivascular adipose tissue-derived advanced glycation end products in a translational pressure overload-induced heart failure model potentially providing an effective therapeutic option for heart failure patients.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 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".