Abstract MP26: Endothelial-derived Microvesicles From Andean Highlanders With Excessive Erythrocytosis Induce A Deleterious Cardiomyocyte Phenotype
Bibliographic record
Abstract
Background: Excessive erythrocytosis (EE), defined as Hb ≥21 g/dL in men and ≥19 g/dL in women, is a pathologic consequence of residing at high altitude (>2500 m) and is common in Andean highlanders. EE is associated with increased cardiovascular risk and cardiac dysfunction. Specifically, EE has been linked to congestive heart failure as well as right ventricular hypertrophy in high altitude dwellers. The mechanisms responsible for diminished cardiac function in adults with EE remain unclear. Endothelial microvesicles (EMVs) play an important role in mediating interaction between the vascular endothelium and cardiac function. The experimental aim of this study was to determine the effects of EMVs isolated from adults with EE on markers of cardiomyocyte fibrosis, hypertrophy and autophagy as well as endothelial nitric oxide synthase (eNOS). Methods: Twenty-four male residents of Cerro de Pasco, Peru (4,340 m) were studied: 12 highlanders without EE (Healthy; age: 40±4 yr; BMI: 26.4±1.7; Hb: 17.4±0.5 g/dL) and 12 highlanders with EE (EE: 45±5 yr; 26.7±1.0; 24.4±0.4 g/dL). All subjects were non-obese, normotensive, normolipidemic and non-diabetic. EMVs (CD31+/CD42b-) were identified, enumerated, and isolated from plasma by flow cytometry. Human induced pluripotent stem cell cardiomyocytes were cultured and treated with EMVs from either healthy or EE men. Results: EMVs from EE men induced significantly greater expression of specific markers of fibrosis: TGF-β (91.1±4.0 vs 52.7±3.8 AU) and alpha-1 type I collagen (85.6±5.6 vs 59.7±4.8 AU) and hypertrophy: troponin T (41.4±2.0 vs 16.9±1.4 AU) and α-actinin (95.3±6.7 vs 62.4±5.0 AU) than EMVs from healthy men. Cell autophagy was not significantly affected by EE EMVs. Intercellular expression of phosphorylated eNOS at the primary activation site, Ser1177 (13.3±1.1 vs 18.9±1.2 AU), and inhibitory site, Thr495 (56.7±3.4 vs 40.8±2.7 AU), were ~35% lower and ~30% higher (both P<0.05), respectively, in cells treated with EMVs from EE compared with healthy men. Conclusions: These data indicate that EMVs from Andean highlanders with EE negatively affect cardiomyocyte function and, therefore, may contribute to the increased risk of heart failure and cardiac dysfunction associated with EE.
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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) | 0.000 | 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) | 0.002 | 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 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".