24-OR: Augmented Heparanase Secretion in Diabetes Regulates Development of Cardiac Hypertrophy
Bibliographic record
Abstract
HSPG consist of a core protein to which several linear heparan sulphate (HS) side chains are linked. Heparanase (Hpa) is exceptional in its ability to degrade HS. This property is used to regulate cardiac metabolism by releasing LPL, for its onward movement to the vascular lumen to hydrolyze lipoprotein-TG for FA provision to the heart. We hypothesized that another function of Hpa is its ability to promote cardiac hypertrophy. Hearts from mice with global overexpression of Hpa appeared larger, had higher heart weight/tibia length ratios, and exhibited posterior wall thickening. This evidence of cardiac hypertrophy was not reflected in alterations in cardiac function; ejection fraction, fractional shortening, and stroke volume were largely unaffected. This suggested a physiological rather than pathological hypertrophy, and is linked to a role for Hpa in regulation of arterial structure and mechanics. Hearts from animals with cardiac-specific overexpression of VEGFB also released greater amounts of Hpa, and this coincided with a hypertrophic phenotype. Heart function in these VEGFB-Tg rats remained similar to wild-type, and was likely a consequence of the expanded coronary vasculature and metabolic reprogramming that favoured glucose utilization. Rats made diabetic with STZ did not show any changes in cardiac Hpa gene or protein expression. Nevertheless, immediately after retrograde perfusion, the diabetic hearts released significantly greater amounts of Hpa with evidence of relative cardiac hypertrophy. This cardiac hypertrophy in diabetic rats was pathological with ventricular wall thinning and reduced cardiac function. Our data imply that Hpa can stimulate cardiac hypertrophy that remains physiological when there is associated development of coronary vasculature with metabolic flexibility. With diabetes and the occurrence of microangiopathy along with metabolic inflexibility, hypertrophy progresses towards being pathological, leading to heart failure. Disclosure C.Lee: None. R.Shang: None. B.Hussein: None. B.Rodrigues: None. Funding Canadian Institutes of Health Research (PJT178134); Heart and Stroke Foundation of Canada (G190026493)
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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) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 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".