Abstract 167: Mapping of Chromosome 2 Regions Linked to Vascular Inflammation Using Congenic Rats
Bibliographic record
Abstract
Background: Immune cells have been implicated in hypertension and vascular inflammation. We demonstrated that chromosome 2 modulates immune responses in genetic hypertension via T regulatory lymphocytes (Treg). Introgression of chromosome 2 from normotensive Brown Norway (BN) rats into hypertensive Dahl salt sensitive (SS) background (consomic SB2) reduced vascular inflammation and restored Treg function. We hypothesized that the BN chromosome 2 contains genes that reduce vascular inflammation, which could be mapped using congenic rats containing portions of BN chromosome 2 on the SS background. Methods: Twelve-to-13 week old male BN, SS, SB2, congenic (SB)A, SBB and SBE rats fed normal salt diet were studied. Systolic blood pressure (SBP) was measured by telemetry. Spleen Treg (CD4 + CD25 hi ) and CD4 + CD25 - T lymphocytes were isolated and characterized by fluorescence-activated cell sorting (FACS) and cultured. Transforming growth factor (TGF)-β, tumor necrosis factor (TNF)-α, interleukin (IL)-10, IL-17 and IL-6 secreted by 10 5 cells in culture media was measured by microbead multiplex immunoassays. Aortic collagen content was determined by Sirius red staining. Results: SS, SB2 and SBE exhibited 20 mmHg higher SBP compared to BN, SBA, and SBB ( P <0.05). The % of CD4 + CD25 - was higher in SS, SB2 and SBE (∼16 %) compared to BN, SBA and SBB (∼12%, P <0.05). The % of Treg was lower in SBA (2%) compared to SS and SB2 (3%, P <0.05). CD4 + CD25 - secretion of TNF-α, IFN-γ and IL-6 was always lower in SS and SBB (≤141, 1428 and 13 pg/10 5 cells, respectively, P <0.05), and consistently unchanged in SB2 and SBE (∼320, 22350 and 50 pg/10 5 cells, respectively) compared to BN (458, 3552 and 57 pg/10 5 cells, respectively). Treg IL-10 and IL-17 production was increased in SB2 (9597 pg/10 5 cells), and SS and SB2 (>90 pg/10 5 cells), respectively ( P <0.05) and unchanged in congenic rats (∼2540 and 23 pg/10 5 cells, respectively), compared to BN (2497 and 9 pg/10 5 cells). Aortic collagen was increased 3-fold in SS, 1.7-fold in SB2 and SBB ( P <0.05) and unchanged in SBA and SBE compared to BN. Conclusion: These results suggest that some of the genes that regulate vascular inflammatory responses are contained within the fragment of chromosome 2 from Brown-Norway rats present in congenic SBE rats.
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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 | 0.001 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.010 | 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".