Epidemiological and histological findings implicate matrix Gla protein in diastolic left ventricular dysfunction
| العنوان: | Epidemiological and histological findings implicate matrix Gla protein in diastolic left ventricular dysfunction |
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| المؤلفون: | Pierre Monney, Tatiana Kuznetsova, Yassine Bouatou, Wen-Yi Yang, Peter Verhamme, Qi-Fang Huang, Pierre-Yves Martin, Karel Allegaert, Cees Vermeer, Jan A. Staessen, Lutgarde Thijs, Murielle Bochud, Sander Trenson, Zhenyu Zhang, Menno Pruijm, Stefan Janssens, Fang-Fei Wei, Belen Ponte, Georg Ehret, Michel Burnier |
| المساهمون: | ACS - Pulmonary hypertension & thrombosis, Graduate School, ACS - Diabetes & metabolism, RS: CARIM - R1.02 - Vascular aspects thrombosis and haemostasis, RS: CARIM - R3.02 - Hypertension and target organ damage, Pediatric Surgery |
| المصدر: | PloS one, vol. 13, no. 3, pp. e0193967 PLoS ONE, 13(3):e0193967. Public Library of Science PLoS ONE PLOS ONE PLOS ONE, 13(3):e0193967. Public Library of Science PLoS One (online), 13(3):e0193967. Public Library of Science PLOS ONE, Vol. 13, No 3 (2018) P. e0193967 PLoS ONE, Vol 13, Iss 3, p e0193967 (2018) |
| بيانات النشر: | Public Library of Science (PLoS), 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | Male, Myocardium/metabolism, medicine.medical_treatment, Organic chemistry, Blood Pressure, Vascular Medicine, Biochemistry, Electrocardiography, Ventricular Dysfunction, Left, 0302 clinical medicine, 80 and over, lcsh:Science, ddc:616, Aged, 80 and over, Extracellular Matrix Proteins, Ventricular Dysfunction, Left/diagnostic imaging/epidemiology/metabolism/pathology, Heart, Vitamins, Physical sciences, Myocardium/metabolism/pathology, Blood, PRESERVED EJECTION FRACTION, ARTERIAL STIFFNESS, Switzerland, MENAQUINONE-7 SUPPLEMENTATION, medicine.medical_specialty, Endothelium, B vitamins, Extracellular Matrix Proteins/metabolism, 03 medical and health sciences, Calcium-Binding Proteins/metabolism, Humans, Aged, Myocardium, lcsh:R, Calcium-Binding Proteins, Biology and Life Sciences, Proteins, nutritional and metabolic diseases, medicine.disease, 030104 developmental biology, Blood pressure, lcsh:Q, Myocardial Ischemia/diagnostic imaging/metabolism/pathology/surgery, K-DEPENDENT PROTECTION, BONE MORPHOGENETIC PROTEIN-4, Adult, Cardiomyopathy, Dilated/diagnostic imaging, Cardiomyopathy, Dilated/metabolism, Cardiomyopathy, Dilated/pathology, Cardiomyopathy, Dilated/surgery, Cohort Studies, Female, Heart/diagnostic imaging, Heart Transplantation, Middle Aged, Multivariate Analysis, Myocardial Ischemia/diagnostic imaging, Myocardial Ischemia/metabolism, Myocardial Ischemia/pathology, Myocardial Ischemia/surgery, Myocardium/pathology, Netherlands, Ventricular Dysfunction, Left/diagnostic imaging, Ventricular Dysfunction, Left/epidemiology, Ventricular Dysfunction, Left/metabolism, Ventricular Dysfunction, Left/pathology, Young Adult, 0301 basic medicine, POWERFUL PREDICTOR, Vitamin K, Physiology, Myocardial Ischemia, lcsh:Medicine, 030204 cardiovascular system & hematology, Matrix gla protein, Ventricular Dysfunction, Medicine and Health Sciences, VITAMIN-K, Post-Translational Modification, Phosphorylation, Dilated/diagnostic imaging, GENERAL-POPULATION, Heart transplantation, Multidisciplinary, biology, Dilated cardiomyopathy, Body Fluids, Chemistry, medicine.anatomical_structure, Cardiology, HEART-FAILURE, Anatomy, Left/diagnostic imaging, Research Article, Cardiomyopathy, Dilated, Histology, Cardiomyopathy, Diastole, Blood Plasma, Chemical compounds, Cardiomyopathy, Dilated/diagnostic imaging/metabolism/pathology/surgery, Internal medicine, Organic compounds, medicine, business.industry, FILLING PRESSURE, Heart failure, Cardiovascular Anatomy, Arterial stiffness, biology.protein, business |
| الوصف: | 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. ispartof: PLoS One vol:13 issue:3 ispartof: location:United States status: published |
| وصف الملف: | application/pdf; Electronic-eCollection |
| تدمد: | 1932-6203 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4aff9ed51157912e174ef7c5dca1da17Test https://doi.org/10.1371/journal.pone.0193967Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....4aff9ed51157912e174ef7c5dca1da17 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
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