Epidemiological and histological findings implicate matrix Gla protein in diastolic left ventricular dysfunction.

Détails

Ressource 1Télécharger: BIB_CB5AA46EEA43.pdf (43819.70 [Ko])
Etat: Public
Version: Final published version
ID Serval
serval:BIB_CB5AA46EEA43
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Epidemiological and histological findings implicate matrix Gla protein in diastolic left ventricular dysfunction.
Périodique
PloS one
Auteur(s)
Wei F.F., Trenson S., Monney P., Yang W.Y., Pruijm M., Zhang Z.Y., Bouatou Y., Huang Q.F., Ponte B., Martin P.Y., Thijs L., Kuznetsova T., Allegaert K., Janssens S., Vermeer C., Verhamme P., Burnier M., Bochud M., Ehret G., Staessen J.A.
ISSN
1932-6203 (Electronic)
ISSN-L
1932-6203
Statut éditorial
Publié
Date de publication
2018
Peer-reviewed
Oui
Volume
13
Numéro
3
Pages
e0193967
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Résumé
A novel paradigm of diastolic left ventricular (LV) dysfunction proposes involvement of the cardiac microvasculature. Vitamin K dependent matrix Gla protein (MGP) plays a role in preserving microcirculatory integrity. We hypothesized that LV filling pressure-a measure of diastolic LV dysfunction-increases with higher plasma level of inactive desphospho-uncarboxylated MGP (dp-ucMGP). We also studied the distribution of active and inactive MGP in human myocardium.
We measured echocardiographic diastolic LV function and plasma dp-ucMGP (ELISA) in 668 Flemish and for replication in 386 Swiss.
Among Flemish and Swiss, E/e' (6.78 vs. 6.73) and dp-ucMGP (3.94 μg/L vs. 4.20 μg/L) were similarly distributed. In multivariable-adjusted models, for each doubling of dp-ucMGP, E/e' increased by 0.26, 0.33 and 0.31 in Flemish, Swiss and both cohorts combined (P≤0.026); the odds ratios for having E/e' ≥ 8.5 were 1.99, 3.29 and 2.36, respectively (P≤0.017). Cardiac biopsies from patients with ischemic or dilated cardiomyopathy and healthy hearts (n = 4 for each) were stained with conformation-specific MGP antibodies. In diseased compared with normal hearts, uncarboxylated inactive MGP was more prevalent (P≤0.004) in the perivascular matrix and interstitium (204.4 vs. 8.6 μm2 per field) and phosphorylated active MGP in and around capillaries and interstitial cells (31.3 vs. 6.6 number of positive capillaries and cells per field).
Our study supports a role of activated MGP in maintaining myocardial integrity and diastolic LV performance and can potentially be translated into new strategies for managing diastolic LV dysfunction and preventing its progression to heart failure.
Mots-clé
Adult, Aged, Aged, 80 and over, Calcium-Binding Proteins/metabolism, Cardiomyopathy, Dilated/diagnostic imaging, Cardiomyopathy, Dilated/metabolism, Cardiomyopathy, Dilated/pathology, Cardiomyopathy, Dilated/surgery, Cohort Studies, Electrocardiography, Extracellular Matrix Proteins/metabolism, Female, Heart/diagnostic imaging, Heart Transplantation, Humans, Male, Middle Aged, Multivariate Analysis, Myocardial Ischemia/diagnostic imaging, Myocardial Ischemia/metabolism, Myocardial Ischemia/pathology, Myocardial Ischemia/surgery, Myocardium/metabolism, Myocardium/pathology, Netherlands, Switzerland, Ventricular Dysfunction, Left/diagnostic imaging, Ventricular Dysfunction, Left/epidemiology, Ventricular Dysfunction, Left/metabolism, Ventricular Dysfunction, Left/pathology, Young Adult
Pubmed
Web of science
Open Access
Oui
Création de la notice
15/03/2018 19:24
Dernière modification de la notice
20/08/2019 16:46
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