Abstract WP255: Cftr Deficiency Increases Systolic Blood Pressure and Exacerbates Cerebrovascular Remodeling in Angiotensin-induced Hypertension
Bibliographic record
Abstract
Introduction: Cystic fibrosis transmembrane conductance regulator (CFTR) functions as a cAMP-dependent chloride channel, has primarily been studied in the secretary epithelia, where the mutation in the CFTR leads to classic CF phenotype. CFTR has been linked to vascular tone regulation and clinical hypotension. The study aims to examine whether CFTR plays a role in cerebrovascular pathological changes during hypertension. Methods: The wild type (WT) and CFTR null mice were implanted with mini-osmotic pumps loaded with Ang II (1000ng/kg/min) to establish Ang-II induced hypertension model. The 2-kidney-2-clip (2k2c), stroke prone hypertensive rats was also applied. Results: There is no significant difference in systolic blood pressure (SBP) and basilar arterial morphological features between WT and CFTR-/- mice. However, after Ang-II infusion, SBP and medial cross-sectional area, media thickness, and media-lumen ratio of the basilar artery was significantly increased in CFTR-/- mice, indicating that CFTR deficiency exacerbates hypertension and cerebrovascular remodeling. The exacerbating cerebrovascular remodeling was confirmed by the disarray of VSMCs and extracellular matrix accumulation using electron microcopy; by enhanced VSMC proliferation using BrdU assay and VSMC differentiation marker gene analysis. Moreover, CFTR protein/mRNA expression in hypertensive basilar arteries was markedly reduced and negatively correlated with the level of SBP. In vitro, Ang-II (100nM) induced BASMCs proliferation and the phenotype switch from a contractile to a proliferative type, accompanied by a decrease in CFTR protein expression. Adenovirus-mediated hCFTR overexpression inhibited, whereas CFTR siRNA enhanced Ang II-induced proliferation and cell cycle transition from G0/G1 to S phase via modulating cyclin D1, cyclin E and p21. Moreover, CFTR was required for AT1R-RhoA-p38 MAPK pathway activated by Ang II, which reduced CFTR channel activation and thus activated AT1R-mediated signaling. Conclusion: Our findings indicated that CFTR deficiency promotes the development of hypertension, which may be ascribed to CFTR negatively modulating hypertension-related VSMC proliferative phenotype switch and cerebrovascular remodeling.
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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 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.009 | 0.001 |
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".