Novel Insights Into Lp(a) Physiology and Pathogenicity: More Questions Than Answers?
Notice bibliographique
Résumé
Lipoprotein(a) (Lp(a)) is of interest to both basic researchers who endeavour to understand the mechanism of action of this unique lipoprotein, as well as to clinicians who are interested in the contribution of Lp(a) to cardiovascular risk profiles. The Lp(a) particle contains a moiety that is indistinguishable from circulating LDL, covalently linked to the unique glycoprotein component apolipoprotein(a) (apo(a)). Since the 1970s, epidemiological data have been accumulated that, on balance, indicate that elevated plasma Lp(a) concentrations are an independent risk factor for vascular diseases. Apo(a) is highly homologous to the fibrinolytic proenzyme plasminogen, containing many tandemly-repeated kringle motifs similar to several of those found in the plasminogen molecule; the size of the kringle domain in apo(a) gives rise to Lp(a) isoform size heterogeneity which is a hallmark of this lipoprotein. The similarity between Lp(a) and plasminogen led to speculation of a bridging role for Lp(a) in atherothrombotic disease based on the duality of the structure of this lipoprotein. In this scenario, LDL would contribute to the proatherosclerotic properties of the particle, while apo(a) would interfere with the normal fibrinolytic functions of plasminogen, thereby inhibiting the breakdown of thrombi formed in the vasculature. Many in vitro and in vivo studies have suggested a prothrombotic role for Lp(a) which is attributable to the apo(a) component of the particle. However, there are a number of unique properties that apo(a) confers to Lp(a) which are independent of its similarity to plasminogen. These include the ability of apo(a)/Lp(a) to affect platelet function, to contribute to endothelial dysfunction, and to inhibit the clearance of chylomicron remnant particles in a transgenic mouse model. Very recent data have revealed a potential role for Lp(a) in the preferential binding of oxidized phospholipid adducts through one of the kringle motifs in apo(a). Many questions remain to be answered regarding the role of Lp(a) in atherothrombotic disease. This article will review the relevant literature concerning the contribution of Lp(a) to risk for both atherosclerotic and purely thrombotic disorders, as well as the proposed mechanisms of Lp(a) pathogenicity related to the structure of this lipoprotein. Emerging areas of interest in the field including the role of apo(a) isoform size as a risk factor for CHD - independent of Lp(a) levels - will also be discussed, as will speculation as to the possible physiological role of Lp(a). Future directions in the field as well as recommendations for the use of Lp(a) in clinical contexts will also be addressed.
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 | 0,001 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,002 | 0,001 |
| Méta-épidémiologie (sens large) | 0,009 | 0,009 |
| Bibliométrie | 0,000 | 0,001 |
| Études des sciences et des technologies | 0,001 | 0,001 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,001 | 0,001 |
| Intégrité de la recherche | 0,002 | 0,002 |
| 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; les deux têtes enseignantes s’accordent sur ce qui est montré ici.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».