serval:BIB_CB5AA46EEA43
Epidemiological and histological findings implicate matrix Gla protein in diastolic left ventricular dysfunction.
10.1371/journal.pone.0193967
000427189300037
29529056
Wei
F.F.
author
Trenson
S.
author
Monney
P.
author
Yang
W.Y.
author
Pruijm
M.
author
Zhang
Z.Y.
author
Bouatou
Y.
author
Huang
Q.F.
author
Ponte
B.
author
Martin
P.Y.
author
Thijs
L.
author
Kuznetsova
T.
author
Allegaert
K.
author
Janssens
S.
author
Vermeer
C.
author
Verhamme
P.
author
Burnier
M.
author
Bochud
M.
author
Ehret
G.
author
Staessen
J.A.
author
article
2018
PloS one
1932-6203
1932-6203
journal
13
3
e0193967
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.
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
eng
60_published
true
peer-reviewed
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
University of Lausanne
mailto:serval_help@unil.ch
http://www.unil.ch/serval
http://serval.unil.ch/disclaimer
https://serval.unil.ch/notice/serval:BIB_CB5AA46EEA43