Alterations in the Eicosanoid Profile and Mitochondrial Injury in Human Ventricular Tissue Following Myocardial Infarction
Notice bibliographique
Résumé
Study objective Myocardial infarction (MI) accounts for a significant proportion of death and disability in the ageing population. n‐6 PUFAs linoleic acid and arachidonic acid have come under investigation for their role in mediating a cardiac response following ischemic injury. CYP450 metabolism of these fatty acids results in formation of numerous metabolites, called eicosanoids, which can be further metabolised by the enzyme soluble epoxide hydrolase (sEH). These lipid mediators exhibit a wide range of cellular effects including alterations to mitochondria structure and function which may impact cardiac performance. This study investigated alterations to CYP‐derived eicosanoids and mitochondria in heart tissue obtained from individuals who experienced a previous MI. Methods Samples were obtained from male and female individuals included in the Human Explanted Heart Program and correlated to non‐failing control hearts (NFC) collected from unused transplant donors through the Human Organ Procurement and Exchange Program at the University of Alberta. Ventricular tissues were harvested from patients who had previously experienced a LAD infarct (≥2yrs), as determined by echocardiography, ECG and coronary angiograms. Protein expression was determined by immunoblotting techniques. Mitochondrial enzymatic activities were assessed by spectrophotometric methods while mitochondrial ultrastructure and cristae density were assessed by electron microscopy. A metabolic profile in ventricular tissue was obtained by LCMS. Results Marked differences in both LA and AA metabolic profiles were revealed in post‐MI tissues. There were significant increases in cardiotoxic metabolites correlating with decreased cardiac function and injury. Interestingly, there was a significant increase in both sEH activity and expression in post‐MI tissues compared to NFC. Expression of mitochondrial proteins remained unchanged, however enzymatic function declined in post‐MI tissues compared to NFC correlating with marked disruption in mitochondrial ultrastructure. Conclusions These data provide the first evidence demonstrating a marked shift in eicosanoid metabolism in post‐MI hearts that correlates with mitochondrial structural disruption and overall decreased mitochondrial function. Support or Funding Information Support for this project was provided by the Canadian Institutes of Health Research. KL Jamieson is supported by funding from Alberta Innovates‐Health Solutions. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .
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) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 0,000 |
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 ».