Abstract 17982: Krippel-Like Transcription Factor- 2 Preserves Endothelial Function and Protects Against Pulmonary Hypertension
Bibliographic record
Abstract
RATIONALE: Pulmonary Hypertension (PH) is associated with ongoing endothelial cell (EC) dysfunction. Shear-responsive Krüppel-like Transcription Factor- 2 (KLF2) is thought to maintain EC homeostasis and to enhance NO bioavailability by inducing eNOS transcription and decreasing caveolin-1 expression. Thus, we hypothesized that KLF2 expression would be reduced in experimental PH, and KLF2 overexpression would prevent pulmonary arterial (PA) remodeling and preserve EC function in chronic hypoxia (CH)-induced PH. METHODS: Lung KLF2 mRNA levels were measured at 1, 3, 7, or 21 days in the CH (10% O2) rat model of PH. Selective gene transfer of KLF2 or empty plasmid to lung ECs was achieved by intravenous injection of jetPEI™ with plasmid DNA (150µg) at day 3 of CH. At 21 days of CH, right ventricular systolic pressure (RVSP), RV hypertrophy, and medial area in PAs with external diameters of <30µm and 30-50µm were assessed. Ex vivo lung functional analyses were performed and eNOS expression was assessed 24 hrs after shKLF2 delivery. RESULTS: KLF2 mRNA expression was reduced at 3 days of CH (0.3±0.1;P<0.05; normalized to sham), returning to control levels at 7 and 21 days. Compared with control transfection, KLF2 gene therapy reduced RVSP (69.5 ± 6.5 vs. 46.5 ± 2.6 mmHg; P<0.01; n=11-13) and RV/LV+S weight ratios (0.35 ± 0.02 vs. 0.28 ± 0.01, n=11-13; P<0.05), associated with a 1.3 fold increase in lung eNOS expression (P=0.04), but no change in PA medial area at day 21. Moreover, KLF2 knockdown resulted in increased RVSP in normoxic rats, matched with reduced eNOS expression to 0.60 ± 0.08 fold and a blunted vasodilator response to ACh (-4.68 ± 0.99 vs. -7.17 ± 0.80 ⋔mmHg; P<0.01; n=6), while SNP-induced dilation was unchanged (n=4) compared to transfected controls (RS). CONCLUSIONS: These results suggest that KLF2 is protective in the CH model of PH. The mechanism of protection involved maintenance of eNOS expression and endothelial dilatory function, rather than vascular remodeling.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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) | 0.001 | 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) | 0.006 | 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".