Wnt5a is associated with right ventricular dysfunction and adverse outcome in dilated cardiomyopathy
Abstract The Wingless (Wnt) pathway has been implicated in the pathogenesis of dilated cardiomyopathy (DCM). To explore the role of Wnt modulators Wnt5a and sFRP3 in DCM patients we analyzed the expression of Wnt5a and sFRP3 in plasma and myocardium of DCM patients and evaluated their effects on NFA...
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2017-06-01
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doaj-572165425058480c879552c9e58ac6e12020-12-08T01:32:30ZengNature Publishing GroupScientific Reports2045-23222017-06-017111010.1038/s41598-017-03625-9Wnt5a is associated with right ventricular dysfunction and adverse outcome in dilated cardiomyopathyAurelija Abraityte0Ida G. Lunde1Erik T. Askevold2Annika E. Michelsen3Geir Christensen4Pål Aukrust5Arne Yndestad6Arnt Fiane7Arne Andreassen8Svend Aakhus9Christen P. Dahl10Lars Gullestad11Kaspar Broch12Thor Ueland13Research Institute of Internal Medicine, Oslo University HospitalCenter for Heart Failure Research, University of OsloResearch Institute of Internal Medicine, Oslo University HospitalResearch Institute of Internal Medicine, Oslo University HospitalCenter for Heart Failure Research, University of OsloResearch Institute of Internal Medicine, Oslo University HospitalResearch Institute of Internal Medicine, Oslo University HospitalFaculty of Medicine, University of OsloDepartment of Cardiology, Oslo University HospitalDepartment of Cardiology, Oslo University HospitalResearch Institute of Internal Medicine, Oslo University HospitalFaculty of Medicine, University of OsloDepartment of Cardiology, Oslo University HospitalResearch Institute of Internal Medicine, Oslo University HospitalAbstract The Wingless (Wnt) pathway has been implicated in the pathogenesis of dilated cardiomyopathy (DCM). To explore the role of Wnt modulators Wnt5a and sFRP3 in DCM patients we analyzed the expression of Wnt5a and sFRP3 in plasma and myocardium of DCM patients and evaluated their effects on NFAT luciferase activity in neonatal mouse cardiomyocytes. Elevated circulating Wnt5a (n = 102) was associated with increased pulmonary artery pressures, decreased right ventricular function and adverse outcome, with a stronger association in more severely affected patients. A higher Wnt5a/sFRP3 ratio (n = 25) was found in the right ventricle vs. the left ventricle and was correlated with NFAT activation as well as pulmonary artery pressures. Wnt5a induced NFAT activation and sFRP3 release in cardiomyocytes in vitro, while sFRP3 antagonized Wnt5a. Wnt5a is associated with right ventricular dysfunction and adverse outcome in DCM patients and may promote the progression of DCM through NFAT signaling.https://doi.org/10.1038/s41598-017-03625-9 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Aurelija Abraityte Ida G. Lunde Erik T. Askevold Annika E. Michelsen Geir Christensen Pål Aukrust Arne Yndestad Arnt Fiane Arne Andreassen Svend Aakhus Christen P. Dahl Lars Gullestad Kaspar Broch Thor Ueland |
spellingShingle |
Aurelija Abraityte Ida G. Lunde Erik T. Askevold Annika E. Michelsen Geir Christensen Pål Aukrust Arne Yndestad Arnt Fiane Arne Andreassen Svend Aakhus Christen P. Dahl Lars Gullestad Kaspar Broch Thor Ueland Wnt5a is associated with right ventricular dysfunction and adverse outcome in dilated cardiomyopathy Scientific Reports |
author_facet |
Aurelija Abraityte Ida G. Lunde Erik T. Askevold Annika E. Michelsen Geir Christensen Pål Aukrust Arne Yndestad Arnt Fiane Arne Andreassen Svend Aakhus Christen P. Dahl Lars Gullestad Kaspar Broch Thor Ueland |
author_sort |
Aurelija Abraityte |
title |
Wnt5a is associated with right ventricular dysfunction and adverse outcome in dilated cardiomyopathy |
title_short |
Wnt5a is associated with right ventricular dysfunction and adverse outcome in dilated cardiomyopathy |
title_full |
Wnt5a is associated with right ventricular dysfunction and adverse outcome in dilated cardiomyopathy |
title_fullStr |
Wnt5a is associated with right ventricular dysfunction and adverse outcome in dilated cardiomyopathy |
title_full_unstemmed |
Wnt5a is associated with right ventricular dysfunction and adverse outcome in dilated cardiomyopathy |
title_sort |
wnt5a is associated with right ventricular dysfunction and adverse outcome in dilated cardiomyopathy |
publisher |
Nature Publishing Group |
series |
Scientific Reports |
issn |
2045-2322 |
publishDate |
2017-06-01 |
description |
Abstract The Wingless (Wnt) pathway has been implicated in the pathogenesis of dilated cardiomyopathy (DCM). To explore the role of Wnt modulators Wnt5a and sFRP3 in DCM patients we analyzed the expression of Wnt5a and sFRP3 in plasma and myocardium of DCM patients and evaluated their effects on NFAT luciferase activity in neonatal mouse cardiomyocytes. Elevated circulating Wnt5a (n = 102) was associated with increased pulmonary artery pressures, decreased right ventricular function and adverse outcome, with a stronger association in more severely affected patients. A higher Wnt5a/sFRP3 ratio (n = 25) was found in the right ventricle vs. the left ventricle and was correlated with NFAT activation as well as pulmonary artery pressures. Wnt5a induced NFAT activation and sFRP3 release in cardiomyocytes in vitro, while sFRP3 antagonized Wnt5a. Wnt5a is associated with right ventricular dysfunction and adverse outcome in DCM patients and may promote the progression of DCM through NFAT signaling. |
url |
https://doi.org/10.1038/s41598-017-03625-9 |
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