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

TitleEpidemiological and histological findings implicate matrix Gla protein in diastolic left ventricular dysfunction.
Publication TypeJournal Article
Year of Publication2018
AuthorsWei, 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, JA
JournalPLoS One
Date Published2018
Keywords80 and over, Adult, Aged, Calcium-Binding Proteins/metabolism, Cardiomyopathy, Cohort Studies, Dilated/diagnostic imaging, Dilated/metabolism, Dilated/pathology, Dilated/surgery, Electrocardiography, Extracellular Matrix Proteins/metabolism, Female, Heart Transplantation, Heart/diagnostic imaging, Humans, Left/diagnostic imaging, Left/epidemiology, Left/metabolism, Left/pathology, 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, Young Adult

OBJECTIVES: 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.

METHODS: We measured echocardiographic diastolic LV function and plasma dp-ucMGP (ELISA) in 668 Flemish and for replication in 386 Swiss.

RESULTS: 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).

CONCLUSIONS: 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.

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Alternate JournalPLoS ONE
Citation Key / SERVAL ID8664
Peer reviewRefereed
PubMed ID29529056


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