Abstract 4: Transient Receptor Potential Melastatin 7 Cation Channel (TRPM7) Kinase Domain - a New Player in Angiotensin II-induced Hypertension and Cardiac Hypertrophy
Bibliographic record
Abstract
Transient receptor potential melastatin 7 (TRPM7) cation channel is a unique protein that has the dual ability to act as a channel to regulate transmembrane Mg 2+ transport and also as a kinase to promote cellular signaling. Despite increasing awareness of the importance of Mg 2+ in cardiovascular biology nothing is known about TRPM7 and its kinase domain in the pathophysiology of hypertension. We previously demonstrated that Ang II regulates TRPM7 in vitro . Here we studied TRPM7 kinase-deficient mice to explore the role of the TRPM7 kinase domain in Ang II-induced hypertension. TRPM7 kinase deficient mice (TRPM7 +/- ) and wild type (WT) counterparts were infused with Ang II (400 ng/kg/min; minipumps) for 4 weeks. Blood pressure (BP) was measured by tail cuff. Vascular reactivity and structure studies were performed by myography in mesenteric arteries. Although baseline BP tended to be higher in TRPM7 +/- versus WT mice (127 ± 6.0 vs 119 ± 2.2 mmHg), significance was not achieved. TRPM7 +/- mice displayed earlier onset of BP increase by Ang II (2 weeks; WT-Ang II: 145 ± 5 vs TRPM7 +/- Ang II: 178 ± 9; mmHg). After 4 weeks, BP was significantly higher in TRPM7 +/- (174 ± 10 mmHg) than in WT mice (147 ± 8 mmHg). Ang II-induced hypertension was associated with cardiac hypertrophy, an effect that was exaggerated in TRPM7 +/- mice (WT: 4.4 ± 0.1; WT-Ang II: 5.0 ± 0.2; TRPM7 +/- : 4.5 ± 0.1; TRPM7 +/- Ang II: 5.7 ± 0.1 g/body weight). Mesenteric arteries from Ang II-infused TRPM7 +/- mice exhibited decreased sensitivity to acetylcholine (pD2; WT-Ang II: 7.6 ± 0.3 vs. TRPM7 +/- Ang II: 6.7 ± 0.4), and reduced maximal relaxation compared to WT mice (WT-Ang II: 88 ± 8% vs TRPM7 +/- Ang II: 59 ± 10%). Ang II induced a leftward shift in the stress-strain relationship for both WT and TRPM7 +/- mice in a similar fashion. Plasma analysis revealed that TRPM7 +/- mice were hypomagnesemic, and that Ang II increased Mg 2+ levels to a greater extent in WT than in TRPM7 +/- mice (WT: 0.65 ± 0.02; WT-Ang II: 0.74 ± 0.04; TRPM7 +/- : 0.60 ± 0.01; TRPM7 +/- Ang II: 0.64 ± 0.02; mmol/L). In conclusion, our findings demonstrate that hypertension, cardiac hypertrophy and endothelial dysfunction are exaggerated by Ang II in TRPM7 +/- hypomagnesemic mice, suggesting a novel role for TRPM7 kinase domain in cardiovascular pathophysiology.
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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) | 0.000 | 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 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 0.002 |
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".