Titre
Epidemiological and histological findings implicate matrix Gla protein in diastolic left ventricular dysfunction.
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Wei, F.F.
Auteure/Auteur
Trenson, S.
Auteure/Auteur
Monney, P.
Auteure/Auteur
Yang, W.Y.
Auteure/Auteur
Pruijm, M.
Auteure/Auteur
Zhang, Z.Y.
Auteure/Auteur
Bouatou, Y.
Auteure/Auteur
Huang, Q.F.
Auteure/Auteur
Ponte, B.
Auteure/Auteur
Martin, P.Y.
Auteure/Auteur
Thijs, L.
Auteure/Auteur
Kuznetsova, T.
Auteure/Auteur
Allegaert, K.
Auteure/Auteur
Janssens, S.
Auteure/Auteur
Vermeer, C.
Auteure/Auteur
Verhamme, P.
Auteure/Auteur
Burnier, M.
Auteure/Auteur
Bochud, M.
Auteure/Auteur
Ehret, G.
Auteure/Auteur
Staessen, J.A.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
1932-6203
Statut éditorial
Publié
Date de publication
2018
Volume
13
Numéro
3
Première page
e0193967
Peer-reviewed
Oui
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
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.
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.
Sujets
PID Serval
serval:BIB_CB5AA46EEA43
PMID
Open Access
Oui
Date de création
2018-03-15T17:24:16.769Z
Date de création dans IRIS
2025-05-21T03:04:02Z
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Nom
BIB_CB5AA46EEA43.pdf
Version du manuscrit
published
Taille
42.79 MB
Format
Adobe PDF
PID Serval
serval:BIB_CB5AA46EEA43.P001
URN
urn:nbn:ch:serval-BIB_CB5AA46EEA431
Somme de contrôle
(MD5):de77bc96035ce381e2871d5418832554