Endothelium and Cardiovascular Complications of Diabetes Mellitus: the Role of the Glyoxalase System
Bibliographic record
Abstract
In patients with diabetes, hyperglycemia leads to functional impairment of endothelial cells (ECs) and microangiopathy. Inflammation and endothelial dysfunction (ED) have been associated with the development of several cardiovascular complications. Concentration of methylglyoxal (MG) - a highly reactive aldehyde is increased in diabetes. In a non-pathological state, MG is detoxified by the enzymes glyoxalase-1 (GLO1) and glyoxalase 2 in presence of glutathione. This thesis examines the role of MG accumulation in ECs and bone marrow cells (BMCs), with the consequences it has for their function. To this end, a transgenic mouse model was used in which the human enzyme GLO1 is overexpressed in the vasculature By using a GLO1 overexpressing mouse model studies described here examined the contribution of MG-induced inflammation in vivo to cardiovascular complications of diabetes, namely diabetic heart failure and peripheral vascular disease. This study confirmed that accumulation of MG leads to inflammation and cell death, and further explained how MG affects the role of ECs in development of the heart failure and BMCs in the revascularization. Overexpression of GLO1 in the vasculature diminished MG-induced inflammation, reduced EC death and delayed and limited the loss of cardiac function in streptozotocin (STZ)-induced diabetic mice (Chapter 2). The in vitro part of this study showed that MG and tumor necrosis factor (TNF- have a synergistic effect on cell death (Chapter 3). Overexpressing the GLO1 in BMCs only, restored neovascularization in ischaemic tissue of mice with STZ-induced diabetes (Chapter 4). Taken together, the results of this thesis suggest that hyperglycemia increased MG leads to endothelial inflammation, EC death and decreased angiogenic potential of BMCs. Furthermore, this MG-induced inflammation and reduced cell function observed, identifies a potential target for therapy of the cardiovascular complications seen in diabetes.
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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 | 0.003 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.002 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 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".