Abstract 372: Role of Redox-Sensitive Calcium Channel TRPM2 and Oxidative Stress in Vascular Smooth Muscle Cell Differentiation to an Osteogenic Phenotype: Implications in Hypertension.
Bibliographic record
Abstract
Vascular smooth muscle cell (VSMC) transformation to an osteoblast-like phenotype is a major factor contributing to vascular calcification, often associated with chronic kidney disease and hypertension. Exact molecular mechanisms underlying VSMC transformation remain unclear but intracellular calcium and ROS have been implicated. Whether these factors are interlinked is unknown. Here, we tested the hypothesis that ROS and redox-sensitive calcium channels (TRPM2) induce an osteogenic phenotype transition in VSMCs from WKY and SHRSP rats. Cultured VSMCs from WKY and SHRSP rats were exposed to calcification medium (CaM) (Ca2+ 1.8 mmol/L, PO4 2.0 mmol/L) for 10 days in the presence/absence of tempol (superoxide dismutase mimetic), and N-(p-amylcinnamoyl)anthranilic acid (ACA, TRPM2 inhibitor). Osteocalcin (OC), BMP-2, BMP-7, TRPM2 and TRPM2-S expression, as well as p47 phox translocation (cytosol:membrane), were determined by immunoblotting. ROS generation was evaluated by chemioluminescence. ROS production (Ctl: 30 AU/ug protein; CaM: 60 AU/ug protein, p<0.05) and p47 translocation (Ctl: 0.7 AU; CaM: 1.1AU, p<0.05) were increased by the CaM in VSMCs from WKY. CaM-induced increase in OC (Ctl: 5 AU; CaM: 13 AU) and BMP-2 (Ctl: 0.60 AU; CaM: 0.75AU) (p<0.05), followed by a decrease in BMP-7 (Ctl: 1.12 AU; CaM: 0.7 AU) (p<0.05), expression in VSMCs from WKY; an effect that was inhibited by tempol and ACA. In SHRSP, the increase in OC (Ctl: 1.25 AU; CaM: 2 AU) and BMP-2 (Ctl: 0.6 AU; CaM: 0.85 AU, p<0.05) expression induced by the CaM was also blocked by tempol. TRPM2 expression was higher in SHRSP (1.40 AU) than in WKY (1.05 AU) VSMCs (p<0.05). However, TRPM2-S expression, an intracellular inhibitor of TRPM2, was decreased in SHRSP compared to WKY VSMCs (SHRSP: 0.9 AU; WKY: 1.5 AU; p<0.05), and it was further decreased by the CaM (0.6 AU). In conclusion, ROS, through TRPM-2 sensitive mechanisms, seems to play an important role in VSMC transformation to an osteogenic, a phenomenon that may be exacerbated in hypertension.
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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".