Acute-phase serum amyloid A: Perspectives on its physiological and pathological roles
Notice bibliographique
Résumé
Serum amyloid A (SAA), a protein originally of interest primarily to investigators focusing on AA amyloidogenesis, has become a subject of interest to a very broad research community. SAA is still a major amyloid research topic because AA amyloid, for which SAA is the precursor, is the prototypic model of in vivo amyloidogenesis and much that has been learned with this model has been applicable to much more common clinical types of amyloid. However, SAA has also become a subject of considerable interest to those studying (i) the synthesis and regulation of acute phase proteins, of which SAA is a prime example, (ii) the role that SAA plays in tissue injury and inflammation, a situation in which the plasma concentration of SAA may increase a 1000-fold, (iii) the influence that SAA has on HDL structure and function, because during inflammation the majority of SAA is an apolipoprotein of HDL, (iv) the influence that SAA may have on HDL's role in reverse cholesterol transport, and therefore, (v) SAA's potential role in atherogenesis. However, no physiological role for SAA, among many proposed, has been widely accepted. None the less from an evolutionary perspective SAA must have a critical physiological function conferring survival-value because SAA genes have existed for at least 500 million years and SAA's amino acid sequence has been substantially conserved. An examination of the published literature over the last 40 years reveals a great deal of conflicting data and interpretation. Using SAA's conserved amino acid sequence and the physiological effects it has while in its native structure, namely an HDL apolipoprotein, we argue that much of the confounding data and interpretation relates to experimental pitfalls not appreciated when working with SAA, a failure to appreciate the value of physiologic studies done in the 1970-1990 and a current major focus on putative roles of SAA in atherogenesis and chronic disease. When viewed from an evolutionary perspective, published data suggest that acute-phase SAA is part of a systemic response to injury to recycle and reuse cholesterol from destroyed and damaged cells. This is accomplished through SAA's targeted delivery of HDL to macrophages, and its suppression of ACAT, the enhancement of neutral cholesterol esterase and ABC transporters in macrophages. The recycling of cholesterol during serious injury, when dietary intake is restricted and there is an immediate and critical requirement of cholesterol in the generation of myriads of cells involved in inflammation and repair responses, is likely SAA's important survival role. Data implicating SAA in atherogenesis are not relevant to its evolutionary role. Furthermore, in apoE(-/-) mice, domains near the N- and C- termini of SAA inhibit the initiation and progression of aortic lipid lesions illustrating the conflicting nature of these two sets of data.
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 distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| 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) | 0,000 | 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 tête enseignante, 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 ».