Increased acute vascular deposition of radioactive phosphate is an index of calcification
Bibliographic record
Abstract
Mineral bone disorder and vascular calcification (VC) are substantial contributors to the elevated cardiovascular disease (CVD) burden in chronic kidney disease patients. The degree to which the uremic milieu and mineral dysregulation individually contribute to this CVD is poorly understood. Calcitriol, the active form of vitamin D, is a key regulator of mineral metabolism. In this study, we present a model of rapid calcitriol‐induced VC in rats with normal kidney function, with findings that point to active and non‐active processes of calcification being fundamentally different phenotypes. Male Sprague Dawley rats (n=17, 15 weeks) were injected with 0.5 μg/kg/day calcitriol SQ for 8 days. On the 9th day, half of the animals were sacrificed (n=8, CxE), and the remainder were sacrificed 14 days after the cessation of calcitriol (n=9, CxL). Control animals (n=6) followed the same protocol. Circulating calcium, phosphate, and hormones regulating mineral metabolism (parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF‐23)) were measured every two days. At sacrifice, animals underwent an IV infusion of 300μmol PO4 spiked with radioactive 33 PO 4 . Forty body tissues, including 14 across the vascular tree, were harvested and analyzed for mineral content/VC (calcium and phosphate) as well as acute phosphate deposition ( 33 PO 4 accrual). Daily administration of high‐dose calcitriol significantly elevated FGF‐23 and calcium, and suppressed PTH after only 2 doses, however, 14 days after calcitriol withdrawal, the analytes had fully normalized (Figure 1). Substantial VC was generated over the 8 days of treatment (7.8±4.2 v. 166±142 nmol Ca/mg tissue, p<0.001) and persisted 14 days after stopping treatment (540±492 nmol Ca/mg tissue). Following IV infusion of phosphate labelled with 33 PO 4 , animals sacrificed directly following calcitriol treatment (CxE) had greater accrual of phosphate acutely in the vascular bed compared to those sacrificed 14 days after the cessation of treatment (CxL; −50.4%, p<0.001), despite having sustained levels of resident VC (Figure 2). Despite the similar magnitude of VC, acute deposition of phosphate following the IV load, a potential measure of calcification activity, was significantly greater during calcitriol treatment (CxE) than after stopping it (CxL). This suggests that the VC itself does not mediate the increased accrual of phosphate, but rather the cellular phenotype of the tissue. Also, it was this acute activity, not the resident VC, that aligned with dysregulated mineral metabolism markers. The transcriptional, cellular, and physiological differences of these two states, as well as their differential associations with circulating analytes are not currently differentiated in VC research. These differences likely have an important role in VC present in humans. Support or Funding Information This research was funded by Canadian Institutes of Health Research and Vanier Canada Graduate Scholarships. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".