The Impact of Hypercholesterolemia on Tendon Injury Repair
Notice bibliographique
Résumé
Background Hypercholesterolemia is a condition characterized by high blood cholesterol levels and is associated with tendon xanthomas (cholesterol deposits found on superficial tendons). Lipid accumulation in the tendon's extracellular spaces 1 may disrupt the parallel organization of collagen substructures within the tendon, and negatively affect its mechano‐sensing and mechanical properties, which may lead to injury. We hypothesized that tendon strength and metabolism would be inferior in a high cholesterol environment and attenuate the tendon's ability to repair after injury. Methods 50 Sprague‐Dawley (SD, control) and 50 apolipoprotein E knock‐out rats (ApoE, Envigo, IL, USA) rats bred in‐house were subject to a unilateral patellar tendon (PT) injury at 12 weeks of age; the uninjured limb served as a control. Animals were euthanased at 3, 14 or 42 days post‐injury, time‐points chosen to represent tendon inflammatory, reparative and remodelling repair phases, respectively. Animals were randomly assigned for investigating gene expression (SD/ApoE per timepoint n=4/4), tissue histology (n=6/6), biomechanical testing (n=10/10; 14 and 42 days only). Equal male/female ratios were used where possible (total SD M23/F27, ApoE M23/F26). Results ApoE total cholesterol was over double that of SD rats (mean 2.12 vs 0.99 mg/ml, p<0.001). Despite this, there was little histological evidence of lipid content (Oil Red‐O staining) in tendons of either group, and no apparent differences in tendon mechanical or material properties (Fig. 1). However, there were differences in gene expression (Fig. 2). ApoE rats demonstrated significantly greater COX2 expression than SD; other inflammatory markers (TGFβ, IL‐1, IL‐6) did not differ between groups. COL1A1, SCX, LOXα were significantly upregulated 14 days post injury in SD compared to ApoE. A greater COL3A1 response was also observed in ApoE compared to SD rats. Discussion We found differences in injury repair at the cellular level, using an ApoE high cholesterol model. There was little evidence of lipid accumulation at the tissue level, therefore the PT may have been a poor choice for an injury study in this instance and it is not surprising that biomechanical differences were not found. Moreover, ApoE rats were recently found to demonstrate only modest early atherosclerotic characteristics 2 , thus the young age of our cohort may be a primary factor in the lack of physical evidence of lipid accumulation. Nonetheless, our results indicate that even with a mild phenotype, high cholesterol significantly modulates tendon inflammatory and healing cellular activity, as indicated by altered mRNA levels, which may contribute to the known consequences of tendon cholesterol on tendons in humans. References 1 Grewal et al. 2014. Accumulation of oxidized LDL in the tendon tissues of C57BL/6 or apolipoprotein E knock‐out mice that consume a high fat diet: potential impact on tendon health. PLoS One 9(12): e114214. 2 Rune et al., 2018. Long‐term Western diet fed apolipoprotein E‐deficient rats exhibit only modest early atherosclerotic characteristics. Sci Rep 8(1): 5416.
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 ».