Abstract 348: Angiotensin 1-7 Exerts Protective Effects In Thoracic Aortic Aneurysm By Attenuating Smooth Muscle Cell Phenotypic Switching
Bibliographic record
Abstract
Background: Thoracic aortic aneurysm (TAA) involves extracellular matrix (ECM) remodeling of the aortic wall, leading to reduced biomechanical support with risk of aortic dissection and rupture. Elusive pathophysiology of initiation and progression of TAA has hindered efforts to develop pharmacological therapeutic interventions to delay or prevent progressive aortic dilatation. Activation of the renin-angiotensin system, and resultant Angiotensin (Ang) II synthesis, is critically involved in the onset and progression of TAA. The current study investigated the effects of Angiotensin (Ang) 1-7 on a murine model of TAA. Methods & Results: 8-10 weeks old apolipoprotein-deficient mice (ApoEKO) were infused with Ang II (1.44 mg/kg/day) and treated with Ang 1-7 (0.576 mg/kg/day). Echocardiography and histological analyses revealed increased thoracic aortic dilatation, ECM remodeling, perivascular fibrosis, and inflammation in Ang II-treated mice. Infusion of Ang 1-7 led to suppression of Ang II-induced dilatation, remodeling, and inflammation in the thoracic aorta. The immunofluorescence imaging showed reduced α-SMA fluorescence (contractile marker) in vascular smooth muscle cells (VSMCs) of the aortic media indicating phenotypic switching. In response to Ang II, the thoracic VSMCs from ApoEKO mice exhibited phenotypic switching indicated by reduced contractile ( Acta2, Cnn1, Myh11 ) and increased synthetic ( Il-6, Mmp2, Mmp9, Col1a1, Col3a1 ) gene expression. Ki67 staining and flow cytometry analysis showed VSMCs hyperproliferation with Ang II treatment. Ang 1-7 preserved the contractile phenotype of VSMCs and attenuated hyperproliferation. The mitochondrial structure was assessed using MitoTracker Red staining which showed Ang II-induced excessive mitochondrial fission. DHE and MitoSOX Red staining were used to assess the reactive oxygen species (ROS). Ang II-treated thoracic VSMCs demonstrated elevated cellular and mitochondrial ROS generation. Ang 1-7 mitigated Ang II-induced mitochondrial fission and oxidative stress. Conclusion: Ang 1-7 prevented Ang II-induced vascular remodeling and the development of TAA. Enhancing Ang 1-7 actions may provide a novel therapeutic strategy to prevent or delay the progression of TAA.
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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 | 0.000 |
| 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 | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.005 | 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".