Effects of Multimerin 1 on Platelet and Plasma FV as Determined by Calibrated Automated Thrombography.
Notice bibliographique
Résumé
Abstract Multimerin 1 (MMRN1) is a protein that is not found in plasma and that is complexed with factor V (FV) in platelet α-granules. Following thrombin activation, platelet FV and MMRN1 are released, and FV is converted to Va, promoting its dissociation from MMRN1. Recent studies identifying functional overlap between FV/Va binding sites for phospholipids and MMRN1, and unanswered questions about the functional consequences of MMRN1 on platelet FV function, led us to compare how MMRN1 modulates platelet and plasma FV procoagulant functions using calibrated automated thrombograms (CAT). The effects of platelet and exogenous MMRN1 on FV activity were evaluated using samples of platelet poor human plasma or platelet extracts resuspended in FV deficient plasma to equivalent final FV antigen concentrations. Reactions were triggered with a commercial reagent containing saturating concentrations of tissue factor and phospholipids (60:20:20 phosphatidylcholine: phosphatidylserine: phosphatidylethanolamine). These assays were also used to compare the functional properties of FV in MMRN1-immunodepleted and sham-depleted fractions of a soluble platelet protein extract (prepared with calpain inhibitors). The effects of exogenous MMRN1 on platelet-dependent thrombin generation were also evaluated using normal platelets resuspended in FV deficient plasma. In contrast to plasma, platelet fractions (with an equivalent FV antigen content) consistently showed lower peak and total endogenous thrombin potential. Addition of 17 fold molar excess of exogenous MMRN1 (which represents the physiologic ratio of MMRN1 to FV in platelets) to plasma, or to MMRN1 depleted platelet protein extracts, induced similar reductions in thrombin generation, manifested by increases in lag times (p<0.05), and reductions in peak (p<0.05), and total thrombin generation (p<0.05). Higher concentrations of exogenous MMRN1 caused further attenuation. Analogous, dose-dependent, inhibitory effects of MMRN1 were observed on thrombin generation by normal platelets in FV deficient plasma. Further investigations of the thrombin generating potential of platelet FV were done using sham and MMRN1-depleted platelet extracts. While exogenous MMRN1 inhibited platelet FV dependent thrombin generation, sham-depleted platelet FV (containing MMRN1) consistently showed higher thrombin generation than the same quantity of FV in MMRN1-depleted platelet extracts, characterized by shorter lag times (p<0.05), higher peak thrombin generation (p<0.05), and increased endogenous thrombin potential (p<0.05). Although the sham-depleted fraction had a similar reduced mobility to the MMRN1 depleted platelet FV, it contained very large forms of platelet FV, linked to MMRN1 via the human FV B-domain cysteine. These data indicate that the pool of platelet FV associated with MMRN1 in vivo has procoagulant function and that MMRN1 has inhibitory effects on thrombin generation. The observed differences in the procoagulant properties of platelet and plasma FV in CAT assays likely result from a partial inhibition of platelet FV by MMRN1 that may be counterbalanced by partial platelet FV activation. The paradoxical effects of MMRN1 depletion on the procoagulant function of platelet FV suggests MMRN1 may have other influences that help preserve platelet FV function in vitro, and possibly also in vivo. The MMRN1 liberated by activated platelets and endothelium in vivo could have local modulating effects on thrombin generation.
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 | 0,001 | 0,001 |
| 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 ».