Increased levels of the megakaryocyte and ...
Type de document :
Compte-rendu et recension critique d'ouvrage
PMID :
Titre :
Increased levels of the megakaryocyte and platelet expressed cysteine proteases stefin A and cystatin A prevent thrombosis
Auteur(s) :
Mezzapesa, Anna [Auteur]
Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research [C2VN]
Bastelica, Delphine [Auteur]
Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research [C2VN]
Crescence, Lydie [Auteur]
Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research [C2VN]
Poggi, Marjorie [Auteur]
Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research [C2VN]
Grino, Michel [Auteur]
Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research [C2VN]
Peiretti, Franck [Auteur]
Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research [C2VN]
Panicot-Dubois, Laurence [Auteur]
Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research [C2VN]
Dupont, Annabelle [Auteur]
Récepteurs nucléaires, maladies cardiovasculaires et diabète - U 1011 [RNMCD]
Valero, René [Auteur]
Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research [C2VN]
Maraninchi, Marie [Auteur]
Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research [C2VN]
Bordet, Jean-Claude [Auteur]
Hospices Civils de Lyon [HCL]
Université Claude Bernard Lyon 1 [UCBL]
Alessi, Marie-Christine [Auteur]
Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research [C2VN]
Dubois, Christophe [Auteur]
Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research [C2VN]
Canault, Matthias [Auteur]
Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research [C2VN]
Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research [C2VN]
Bastelica, Delphine [Auteur]
Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research [C2VN]
Crescence, Lydie [Auteur]
Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research [C2VN]
Poggi, Marjorie [Auteur]
Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research [C2VN]
Grino, Michel [Auteur]
Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research [C2VN]
Peiretti, Franck [Auteur]
Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research [C2VN]
Panicot-Dubois, Laurence [Auteur]
Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research [C2VN]
Dupont, Annabelle [Auteur]
Récepteurs nucléaires, maladies cardiovasculaires et diabète - U 1011 [RNMCD]
Valero, René [Auteur]
Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research [C2VN]
Maraninchi, Marie [Auteur]
Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research [C2VN]
Bordet, Jean-Claude [Auteur]
Hospices Civils de Lyon [HCL]
Université Claude Bernard Lyon 1 [UCBL]
Alessi, Marie-Christine [Auteur]
Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research [C2VN]
Dubois, Christophe [Auteur]
Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research [C2VN]
Canault, Matthias [Auteur]
Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research [C2VN]
Titre de la revue :
Scientific Reports
Pagination :
9631
Éditeur :
Nature Publishing Group
Date de publication :
2019-07
ISSN :
2045-2322
Mot(s)-clé(s) en anglais :
Platelets
Obesity
Obesity
Discipline(s) HAL :
Sciences du Vivant [q-bio]
Sciences du Vivant [q-bio]/Alimentation et Nutrition
Sciences du Vivant [q-bio]/Alimentation et Nutrition
Résumé en anglais : [en]
Increased platelet activity occurs in type 2 diabetes mellitus (T2DM) and such platelet dysregulation likely originates from altered megakaryopoiesis. We initiated identification of dysregulated pathways in megakaryocytes ...
Lire la suite >Increased platelet activity occurs in type 2 diabetes mellitus (T2DM) and such platelet dysregulation likely originates from altered megakaryopoiesis. We initiated identification of dysregulated pathways in megakaryocytes in the setting of T2DM. We evaluated through transcriptomic analysis, differential gene expressions in megakaryocytes from leptin receptor-deficient mice (db/db), exhibiting features of human T2DM, and control mice (db/+). Functional gene analysis revealed an upregulation of transcripts related to calcium signaling, coagulation cascade and platelet receptors in diabetic mouse megakaryocytes. We also evidenced an upregulation (7-to 9.7-fold) of genes encoding stefin A (StfA), the human ortholog of Cystatin A (CSTA), inhibitor of cathepsin B, H and L. StfA/CSTA was present in megakaryocytes and platelets and its expression increased during obesity and diabetes in rats and humans. StfA/CSTA was primarily localized at platelet membranes and granules and was released upon agonist stimulation and clot formation through a metalloprotease-dependent mechanism. StfA/CSTA did not affect platelet aggregation, but reduced platelet accumulation on immobilized collagen from flowing whole blood (1200 s −1). In-vivo, upon laser-induced vascular injury, platelet recruitment and thrombus formation were markedly reduced in StfA1-overexpressing mice without affecting bleeding time. The presence of CA-074Me, a cathepsin B specific inhibitor significantly reduced thrombus formation in-vitro and in-vivo in human and mouse, respectively. Our study identifies StfA/CSTA as a key contributor of platelet-dependent thrombus formation in both rodents and humans.Lire moins >
Lire la suite >Increased platelet activity occurs in type 2 diabetes mellitus (T2DM) and such platelet dysregulation likely originates from altered megakaryopoiesis. We initiated identification of dysregulated pathways in megakaryocytes in the setting of T2DM. We evaluated through transcriptomic analysis, differential gene expressions in megakaryocytes from leptin receptor-deficient mice (db/db), exhibiting features of human T2DM, and control mice (db/+). Functional gene analysis revealed an upregulation of transcripts related to calcium signaling, coagulation cascade and platelet receptors in diabetic mouse megakaryocytes. We also evidenced an upregulation (7-to 9.7-fold) of genes encoding stefin A (StfA), the human ortholog of Cystatin A (CSTA), inhibitor of cathepsin B, H and L. StfA/CSTA was present in megakaryocytes and platelets and its expression increased during obesity and diabetes in rats and humans. StfA/CSTA was primarily localized at platelet membranes and granules and was released upon agonist stimulation and clot formation through a metalloprotease-dependent mechanism. StfA/CSTA did not affect platelet aggregation, but reduced platelet accumulation on immobilized collagen from flowing whole blood (1200 s −1). In-vivo, upon laser-induced vascular injury, platelet recruitment and thrombus formation were markedly reduced in StfA1-overexpressing mice without affecting bleeding time. The presence of CA-074Me, a cathepsin B specific inhibitor significantly reduced thrombus formation in-vitro and in-vivo in human and mouse, respectively. Our study identifies StfA/CSTA as a key contributor of platelet-dependent thrombus formation in both rodents and humans.Lire moins >
Langue :
Anglais
Vulgarisation :
Non
Source :
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