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Epidemiological and histological findings implicate matrix Gla protein in diastolic left ventricular dysfunction.
Wei, Fang-Fei; Trenson, Sander; Monney, Pierre; Yang, Wen-Yi; Pruijm, Menno; Zhang, Zhen-Yu; Bouatou, Yassine; Huang, Qi-Fang; Ponte, Belen; Martin, Pierre-Yves; Thijs, Lutgarde; Kuznetsova, Tatiana; Allegaert, Karel; Janssens, Stefan; Vermeer, Cees; Verhamme, Peter; Burnier, Michel; Bochud, Murielle; Ehret, Georg; Staessen, Jan A.
Afiliación
  • Wei FF; Studies Coordinating Centre, Research Unit Hypertension and Cardiovascular Epidemiology, Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium.
  • Trenson S; Division of Cardiology, University Hospitals Leuven, Leuven, Belgium.
  • Monney P; Department of Cardiology, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland.
  • Yang WY; Studies Coordinating Centre, Research Unit Hypertension and Cardiovascular Epidemiology, Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium.
  • Pruijm M; Department of Nephrology, University Hospital of Lausanne, Lausanne, Switzerland.
  • Zhang ZY; Studies Coordinating Centre, Research Unit Hypertension and Cardiovascular Epidemiology, Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium.
  • Bouatou Y; Department of Pathology, Academisch Medisch Centrum, Universiteit van Amsterdam, Amsterdam, The Netherlands.
  • Huang QF; Studies Coordinating Centre, Research Unit Hypertension and Cardiovascular Epidemiology, Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium.
  • Ponte B; Department of Nephrology, University Hospital of Geneva, Geneva, Switzerland.
  • Martin PY; Department of Nephrology, University Hospital of Geneva, Geneva, Switzerland.
  • Thijs L; Studies Coordinating Centre, Research Unit Hypertension and Cardiovascular Epidemiology, Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium.
  • Kuznetsova T; Studies Coordinating Centre, Research Unit Hypertension and Cardiovascular Epidemiology, Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium.
  • Allegaert K; Research Unit Organ Systems, Department of Development and Regeneration, University of Leuven, Leuven, Belgium.
  • Janssens S; Department of Pediatric Surgery, Erasmus Medical Center, Sophia Children's Hospital, Rotterdam, The Netherlands.
  • Vermeer C; Division of Cardiology, University Hospitals Leuven, Leuven, Belgium.
  • Verhamme P; R&D Group VitaK, Maastricht University, Maastricht, The Netherlands.
  • Burnier M; Research Unit Molecular and Vascular Biology, Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium.
  • Bochud M; Department of Nephrology, University Hospital of Lausanne, Lausanne, Switzerland.
  • Ehret G; Division of Chronic Disease, Institute of Social and Preventive Medicine, University Hospital of Lausanne, Lausanne, Switzerland.
  • Staessen JA; Department of Cardiology, University Hospital of Geneva, Geneva, Switzerland.
PLoS One ; 13(3): e0193967, 2018.
Article en En | MEDLINE | ID: mdl-29529056
ABSTRACT

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.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas de Unión al Calcio / Proteínas de la Matriz Extracelular / Disfunción Ventricular Izquierda / Miocardio Tipo de estudio: Diagnostic_studies / Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged País/Región como asunto: Europa Idioma: En Revista: PLoS One Asunto de la revista: CIENCIA / MEDICINA Año: 2018 Tipo del documento: Article País de afiliación: Bélgica

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas de Unión al Calcio / Proteínas de la Matriz Extracelular / Disfunción Ventricular Izquierda / Miocardio Tipo de estudio: Diagnostic_studies / Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged País/Región como asunto: Europa Idioma: En Revista: PLoS One Asunto de la revista: CIENCIA / MEDICINA Año: 2018 Tipo del documento: Article País de afiliación: Bélgica
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