Increased Coronary Artery Dissection Rate and Severity in Murine Model of Marfan Syndrome
Bibliographic record
Abstract
Purpose Marfan syndrome (MFS) is an autosomal dominant genetic disorder that leads to a variety of clinical presentations ‐ most seriously, aortic root dissection and aneurysm. Spontaneous coronary artery dissection, although rare in the general population, is associated with high rate of mortality and occurs more frequently in MFS patients due to their characteristic arterial wall weakness. MFS patients are often prescribed anti‐hypertensives such as Losartan, an angiotensin II type 1 receptor (ATR1) antagonist, but recent clinical trials have cast doubt on their effectiveness in preventing clinical endpoints. We investigated the rate and severity of coronary artery dissection in a murine model of MFS compared to wild‐type mice. Methods Experimental mice were bred with littermate controls using the common Fbn1 C1039G/+ model of MFS giving rise to wild‐type and MFS groups. At 6 or 22 months of age, hearts were fixed, sectioned and stained with hematoxylin and eosin, Movat's pentachrome and iron stains in order to visualize coronary artery dissection. Dissection was scored using a binary system (dissection or no dissection) and a severity‐weighted system (0 represents no dissection, 1 ‐ slight dissection, 2 ‐ clear dissection, 3 ‐ severe dissection). Results At 6 months of age, we saw an unexpectedly high rate of mild coronary artery dissection in wild‐type mice compared to MFS alone (100% in wild‐type vs. 50% in MFS) but when weighted for severity there was no difference between groups (1.0 for wild‐type vs. 0.88 in MFS). However at 22 months of age, the MFS group displayed a higher rate of dissection compared to wild‐type (80% vs. 33%) as well as an increase in dissection severity (1.6 vs. 0.33, respectively). Conclusions To our knowledge, this is the first genetic mouse model of coronary artery dissection. The unexpectedly high rate of mild dissection in wild‐type mice at 6 months of age (all were scored 1 for slight dissection) may be due to low N values at this time‐point or may be part of normal vessel maturation, unfortunately little study on coronary artery dissection in mice has been conducted. However, the observed increase in both rate and severity in MFS mice at 22 months compared to wild‐type is likely due to vessel wall fragility and elastic fibre fragmentation characteristic of MFS which left coronary arteries susceptible to further damage. Future research into the effects of Losartan treatment on rate and severity of coronary artery dissection should be done. Support or Funding Information This research was funded by CIHR grant awarded to Dr. Pascal N Bernatchez.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| 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 | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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 teacher head, 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".