Abstract 9386: Marfan Syndrome Mouse Model MgΔ <sup>Lpn</sup> Presents Alterations in Glomerular Architecture and Increased Renal Vascular Resistance. Losartan Treatment Attenuates These Phenotypes
Bibliographic record
Abstract
Introduction: Previously, we have shown that mgΔ lpn murine Marfan syndrome (MFS) model with a fibrillin-1 disruption presents increased Metalloproteinase-9 (MMP-9) expression in the cilliary body in eye. MMP-9 has been related to microfibrils degradation. In this study, we examined the fibrillin-1 and MMP-9 distribution in the kidney and their influence on hemodynamics. Hypothesis: The alteration of fibrillin-1 impacts the glomerular architecture and modify renal hemodynamics. Methods: Female mice at 4 months of age were used: MFS mgΔ lpn mice (n=5); mgΔ lpn treated with losartan for 3 months (n=5); and control wild type mice (n=5). The glomerular structure of the kidney was examined by histology. The distribution and quantification of fibrillin-1 and MMP-9 were analyzed by immunofluorescence assay. Blood flow in the aorta and renal artery was monitored with the probe 2SB-T206 of the Transonic Systems, and the cortical micro-hemodynamic of the kidney was examined by SDF video-microscopy (Sidestream Dark Field Imaging). Results: The mgΔ lpn mice showed reduction of fibrillin-1 deposition and an increase in MMP-9 in the entire kidney tissue, including the glomerular structures. In histologic aspects, the glomerulus showed a reduction of the glomerular area, urinary space, and vascular pole area. The reduced glomerulus dimension possibly squeezes the arteriolar system with a subsequent increase of their vascular resistance. In addition, the cortical microvessels showed a significant reduction in blood flow, and there was an increase in the distribution of microvessels with diameters 6 to 8 μm. Blood flow analysis in the mgΔ lpn showed decreased artery renal flow but did not reveal a difference in aorta blood flow when compared to WT animals. These results indicate vascular resistance in the renal artery. Losartan therapy increased fibrillin-1 and decreased MMP-9 quantifications, improved the glomerulus structures and significantly increased the velocity of the microcirculation blood flow. Conclusions: Alterations in fibrillin-1 modify the glomerular structures and impair kidney hemodynamics. Losartan therapy minimized the renal phenotypes.
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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) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.008 | 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".