Abstract 1742: Expression of the Anti-Angiogenic Proteins Angiostatin and Endostatin is Increased in Diabetic Patients and Associated with Impaired Coronary Collateral Formation
Bibliographic record
Abstract
Introduction: Coronary artery disease is the leading cause of mortality in diabetics. Due to the diffuse nature of their disease, diabetics may be at risk for incomplete revascularization, highlighting a potential role for pro-angiogenic therapy in this group. This study investigates molecular mechanisms of angiogenesis in diabetics. Methods: Myocardial tissue was harvested from patients undergoing CABG (non-diabetic (ND) 11, type 2 diabetic (DM) 10). Expression of angiostatin, endostatin, their precursors (plasminogen and collagen XVIII, respectively), enzymes leading to their production (Matrix Metalloprotease (MMP) 2 & 9), and an inhibitor of MMPs (TIMP2) was assessed with western blotting. MMP activity was assessed. Serum levels of angiostatin and endostatin were assayed. Coronary collateralization was graded by Rentrop scoring of angiograms. Results: Plasminogen and collagen XVIII expression were similar between groups. Angiostatin expression trended to increase 1.24-fold (p=0.07) and endostatin expression increased 2.02-fold in DM patients relative to ND (p=0.02). Serum angiostatin was 2.68-fold higher (p=0.03) and endostatin 1.39-fold higher (p=0.04) in diabetics. MMP9 expression was no different between groups, whereas MMP2 expression decreased 1.8-fold in diabetics (p=0.003). MMP2 & 9 activity decreased 1.33-fold (p=0.03) and 1.57-fold (p=0.04), respectively, in diabetics. Coronary collateralization scores were ND 2.1 ± 0.37 vs. DM 1.0 ± 0.4 (p=0.05). Myocardial endostatin expression correlated strongly with %HbA1c (R=0.742, p=0.0001). Myocardial expression of angiostatin and endostatin demonstrated significant negative linear correlations with coronary collateralization (angiostatin R=−0.531, p=0.035, endostatin R=−0.794, p=0.0002). Conclusion: Diabetics exhibit increased levels of the anti-angiogenic proteins angiostatin and endostatin and differential regulation of the enzymes governing their production relative to non-diabetics. Myocardial levels of these proteins show significant correlation to coronary collateralization. These findings offer potential new therapeutic targets for enhancing pro-angiogenic therapy and insight in to the angiogenic impairments seen in diabetes.
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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 | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.003 | 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 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".