Epidemiological and histological findings implicate matrix Gla protein in diastolic left ventricular dysfunction.
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-inc...
| Main Authors: | , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2018-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC5846787?pdf=render |
| _version_ | 1818777912530173952 |
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| author | Fang-Fei Wei Sander Trenson Pierre Monney Wen-Yi Yang Menno Pruijm Zhen-Yu Zhang Yassine Bouatou Qi-Fang Huang Belen Ponte Pierre-Yves Martin Lutgarde Thijs Tatiana Kuznetsova Karel Allegaert Stefan Janssens Cees Vermeer Peter Verhamme Michel Burnier Murielle Bochud Georg Ehret Jan A Staessen |
| author_facet | Fang-Fei Wei Sander Trenson Pierre Monney Wen-Yi Yang Menno Pruijm Zhen-Yu Zhang Yassine Bouatou Qi-Fang Huang Belen Ponte Pierre-Yves Martin Lutgarde Thijs Tatiana Kuznetsova Karel Allegaert Stefan Janssens Cees Vermeer Peter Verhamme Michel Burnier Murielle Bochud Georg Ehret Jan A Staessen |
| author_sort | Fang-Fei Wei |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-18T11:36:22Z |
| format | Article |
| id | doaj.art-7790287efec64f58b254b5d87463ad68 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-18T11:36:22Z |
| publishDate | 2018-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-7790287efec64f58b254b5d87463ad682022-12-21T21:09:29ZengPublic Library of Science (PLoS)PLoS ONE1932-62032018-01-01133e019396710.1371/journal.pone.0193967Epidemiological and histological findings implicate matrix Gla protein in diastolic left ventricular dysfunction.Fang-Fei WeiSander TrensonPierre MonneyWen-Yi YangMenno PruijmZhen-Yu ZhangYassine BouatouQi-Fang HuangBelen PontePierre-Yves MartinLutgarde ThijsTatiana KuznetsovaKarel AllegaertStefan JanssensCees VermeerPeter VerhammeMichel BurnierMurielle BochudGeorg EhretJan A StaessenA 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.http://europepmc.org/articles/PMC5846787?pdf=render |
| spellingShingle | Fang-Fei Wei Sander Trenson Pierre Monney Wen-Yi Yang Menno Pruijm Zhen-Yu Zhang Yassine Bouatou Qi-Fang Huang Belen Ponte Pierre-Yves Martin Lutgarde Thijs Tatiana Kuznetsova Karel Allegaert Stefan Janssens Cees Vermeer Peter Verhamme Michel Burnier Murielle Bochud Georg Ehret Jan A Staessen Epidemiological and histological findings implicate matrix Gla protein in diastolic left ventricular dysfunction. PLoS ONE |
| title | Epidemiological and histological findings implicate matrix Gla protein in diastolic left ventricular dysfunction. |
| title_full | Epidemiological and histological findings implicate matrix Gla protein in diastolic left ventricular dysfunction. |
| title_fullStr | Epidemiological and histological findings implicate matrix Gla protein in diastolic left ventricular dysfunction. |
| title_full_unstemmed | Epidemiological and histological findings implicate matrix Gla protein in diastolic left ventricular dysfunction. |
| title_short | Epidemiological and histological findings implicate matrix Gla protein in diastolic left ventricular dysfunction. |
| title_sort | epidemiological and histological findings implicate matrix gla protein in diastolic left ventricular dysfunction |
| url | http://europepmc.org/articles/PMC5846787?pdf=render |
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