PDE6 Isoforms Are Expressed in Native Endothelium but not in Cultured Cell Lines
Bibliographic record
Abstract
Nitric oxide (NO) is a major component of endothelial regulation of vascular homeostasis.. Diffusion of NO to the underlying vascular smooth muscle cells (VSMCs) will trigger Cyclic GMP (cGMP) production through activation of soluble guanylate cyclase leading to myocyte relaxation. As a second messenger central to numerous signalling pathways, proper control of cGMP level is critical. Although modulation of cGMP levels by phosphodiesterases (PDEs) is well established in smooth muscle through PDE5, few studies have focused in cGMP regulation in endothelial cells. Amongst cGMP‐specific PDEs, PDE5 and PDE9 have been reported in VSMCs and ECs. PDE6, a retina‐restricted cGMP‐specific PDE, has considerable similarities with PDE5, including overlapping. The current study establishes the expression of PDE6 isoforms in endothelial cells and their impact on local cGMP levels. Interestingly, all PDE6 isoforms (α, β and γ) were found in endothelial cell from mouse mesenteric arteries. Complementary approaches provide compelling evidences of the expression of PDE6 isoforms at mRNA and protein levels in native endothelial cells. However, PDE6a and b were not detected in endothelial cell lines. Subcellular distribution of PDE6 and 5 was sought using confocal microscopy. Whilst PDE5‐ and PDE6γ‐associated immunofluorescence was homogeneously distributed, PDE6α and PDE6β appeared preferentially localized within the perinuclear region. Mathematical modeling demonstrated the influence of PDE localization on local cGMP concentrations. Indeed, subcellular endothelial cGMP level following a NO pulse is unsymmetrical, with the peri‐nuclear region showing very little increase in cGMP. These results strongly suggest that PDEs, especially PDE6α and PDE6β, might have an significant impact on cGMP‐mediated cellular pathways in native endothelium through the fine‐tuning of cGMP microdomains. Support or Funding Information Supported by FICM
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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".