Oxidative stress contributes to vascular calcification in patients with chronic kidney disease
Bibliographic record
Abstract
Vascular calcification (VC) is a major cause of mortality in patients with chronic kidney disease (CKD). While elevations in serum phosphorus contribute to VC, we provide evidence here for a major role of oxidative stress (OS) in VC pathogenesis without an apparent increase in serum phosphorus in early CKD. In a rat model for stage 5 CKD (CKD5), we observed 1) robust increases of VC and OS, 2) significant reductions of smooth muscle 22 alpha (SM22α) and calponin, and 3) upregulations in Runt-related transcription factor 2 (RUNX2) and collagen I in vascular smooth muscle cells (VSMCs). Inhibition of OS using MnTMPyP dramatically reduced these events without normalization of hyperphosphatemia. In CKD5 patients with VC (n = 11) but not in those without VC (n = 13), OS was significantly elevated. While the serum levels of calcium and phosphate were not altered in the animal model for early stage CKD (ECKD), OS, VC, SM22α, calponin, RUNX2, collagen I and NADPH oxidase 1 (NOX1) in VSMCs were all significantly changed. More importantly, serum (5%) derived from patients with ECKD (n = 30) or CKD5 (n = 30) induced SM22α and calponin downregulation, and RUNX2, collagen I, NOX1 upregulation along with a robust elevation of OS and calcium deposition in primary rat VSMCs. These alterations were all reduced by MnTMPyP, ML171 (a NOX1 inhibitor), and U0126 (an inhibitor of Erk signaling). Collectively, we provide a comprehensive set of evidence supporting an important role of OS in promoting VC development in CKD patients (particularly in those with ECKD); this was at least in part through induction of osteoblastic transition in VSMCs which may involve the Erk singling. Our research thus suggests that reductions in OS may prevent VC in CKD 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) | 0.000 | 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) | 0.000 | 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".