#3651 Extracellular vesicles from the <i>in vitro</i> AKI model promote cardiac cells stress
Notice bibliographique
Résumé
Abstract Background and Aims Extracellular vesicles (EVs) are blebs released by all cell types, exerting intercellular communication function due to their cargo. EVs have been reported to play a role in the pathophysiology of several diseases, such as cancer, cardiovascular, and renal diseases. However, whether EVs contribute to the pathological crosstalk between the kidney and the heart is unknown. We aimed to characterize EVs from in vivo and in vitro acute kidney disease models and to assess whether they would impact cardiac cellular viability. Method C57Bl/6 male mice (uOttawa Animal Facility Protocol: OHRIe3961-A1 and UFABC animal facility commenting number: 9019180122) left kidney were submitted to 60 minutes of warm ischemia and 1 and 8 days of reperfusion (IR1 and IR8). The sham animals (control) only had the left flank opened. HK-2 cells were exposed to hypoxia for 24 hours, followed by 3 hours of reperfusion (HR). The normoxia cells were kept under 21% O2 throughout the HR period. The AKI in vivo model was validated by histological analysis stained with PAS, BUN, and qPCR for KIM-1, and the HR in vitro models were validated by western blot to HIF-1α. EVs were isolated by ultracentrifugation from the plasma and conditioned medium, and characterized by NTA. H9C2 cells were treated with 6000 EVs/ cell from both biofluids for 48 hours, followed by MTT assays. The results were expressed as mean ± standard deviation and analyzed by t-test and ANOVA, in which p-values < 0.005 were considered statistically significant. Results The IR results indicated that in 24 hours of reperfusion, there was a high acute tubular necrosis in the left kidney (0% vs 60%) followed by tubular atrophy and interstitial fibrosis in 8 days (0% vs 73.66%), KIM-1 was upregulated in the left kidney of both 1 and 8 days of reperfusion groups (Sham: 1 ± 1.22 vs IR1: 434.80 ± 192.55, and IR8d: 162.22 ± 84.74), and there was an impairment of the kidney function in 8 days of reperfusion (Sham: 1.66 ± 0.22 vs IR8d: 2.15 ± 0.15). HK-2 submitted to HR expressed 2-fold more HIF-1α than normoxia cells (Normoxia: 1.00 ± 0.11 vs Hypoxia: 1.93 ± 0.81). Regarding EVs characterization, the IR protocol did not induce changes in the total particles/mL (IR1: 2.54 ± 0.52 and IR8: 2.03 ± 0.51 vs Sham: 2.43 ± 0.54) but promoted the particle size (nm) decrease (IR1: 126.33 ± 2.37 and IR8: 128.90 ± 0.86 vs Sham:154.90 ± 4.80). HR-induced HK-2 cells release 2-fold more EVs with bigger sizes (nm) than the control group (Hypoxia: 14.52 ± 7.47 vs Normoxia: 5.30 ± 1.34 particles/mL) (Hypoxia: 183.92 ± 3.90 nm vs Normoxia: 159.55 ± 10.20 nm). Plasma EVs did not affect the cellular viability of H9C2 cells (Sham: 0.94 ± 0.07, IR1: 1.04 ± 0.10 and IR8: 0.98 ± 0.98 vs Untreated: 1.00 ± 0.09), nevertheless, both normoxic and hypoxic EVs induced the reduction of the cellular viability (Normoxia: 0.85 ± 0.02 and Hypoxia: 0.90 ± 0.04 vs Untreated: 1.00 ± 0.04). Conclusion The present results indicated the accomplishment of the IR model as well as HR. The characterization results suggested that hypoxia stimulates EVs biogenesis, release in renal epithelial cells, and also modification in the size. The MTT results indicated that EVs caused stress in cardiac cells affecting their viability.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,001 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,001 | 0,001 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,004 | 0,001 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».