Abstract 12624: Therapeutic Lymphangiogenesis Improves Diastolic Function by Limiting Cardiac Edema and Fibrosis After Myocardial Infarction
Bibliographic record
Abstract
Little knowledge exists on how cardiac lymphatics respond to myocardial infarction (MI). We investigated the impact of MI on cardiac lymphatic structure and function during the development of chronic heart failure (CHF). We hypothesized that 1) insufficient cardiac lymph drainage may contribute to the deleterious cardiac remodeling post-MI; and 2) therapeutic stimulation of lymphatic growth, or lymphangiogenesis, may reduce chronic myocardial edema and inflammation in this setting. MI was modeled in Wistar rats by coronary occlusion (45 min) followed by reperfusion. Lymphangiogenesis-selective VEGF-C was delivered intramyocardially using slow-release albumin-alginate microparticles. Animals were divided into: sham (n=19), control MI (n=64), and treated MI, receiving low (1.5 μg; n= 54) or high (5 μg; n=26) dose of VEGF-C upon reperfusion. Cardiac function, lymphatics, edema, and levels of infiltrating immune cells were evaluated at 3 and 8 weeks post-MI. We found that control rats displayed lymphatic remodeling with increased lymphatic capillary density but rarefaction of epicardial pre-collector and collector vessels, leading to cardiac lymphatic dysfunction. In accordance with insufficient lymph drainage, chronic myocardial edema and low grade inflammation were found at both 3 and 8 weeks post-MI as determined by gravimetry, MRI T2 imaging, and immunohistochemistry, respectively. VEGF-C treatment led to a dose-dependent increase in lymphatic capillary density (sham, 255±16; con, 267±25; VEGF-C, 362±22 lymphatics/mm 2 ; p<0.05) and reduced rarefaction of pre-collectors and collector vessels. As a consequence, myocardial edema (sham, 75.5±0.1; con, 77.9±0.2; VEGF-C, 77.3±0.1% water content; p<0.05) and macrophage infiltration levels were both significantly reduced. Further, cardiac interstitial fibrosis was completely prevented by 8 weeks, even by low dose VEGF-C (con, 6.0±0.6; VEGF-C, 3.3±0.1% fibrosis; p<0.001), leading to reduced diastolic dysfunction (LVDPVR, LV end-diastolic pressure-volume relation: sham, 0.8±0.1; con, 2.0±0.2; VEGF-C, 1.1±0.1; p<0.001). In conclusion, our data suggest that therapeutic lymphangiogenesis may represent a new therapeutic target in CHF.
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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".