Wnt5a is associated with right ventricular dysfunction and adverse outcome in dilated cardiomyopathy

被引：29

作者：

Abraityte, Aurelija ^{[1
,2
,3
]}

Lunde, Ida G. ^{[3
,4
,5
]}

Askevold, Erik T. ^{[1
,3
]}

Michelsen, Annika E. ^{[1
,2
]}

Christensen, Geir ^{[3
,4
,5
]}

Aukrust, Pal ^{[1
,2
,6
,7
,8
]}

Yndestad, Arne ^{[1
,3
,7
]}

Fiane, Arnt ^{[2
,9
]}

Andreassen, Arne ^{[10
]}

Aakhus, Svend ^{[10
,11
]}

Dahl, Christen P. ^{[1
,3
,10
]}

Gullestad, Lars ^{[2
,3
,10
]}

Broch, Kaspar ^{[10
]}

Ueland, Thor ^{[1
,2
,8
]}

机构：

[1] Oslo Univ Hosp, Rikshosp, Res Inst Internal Med, Oslo, Norway

[2] Univ Oslo, Fac Med, Oslo, Norway

[3] Univ Oslo, Ctr Heart Failure Res, Oslo, Norway

[4] Oslo Univ Hosp, Inst Expt Med Res, Oslo, Norway

[5] Univ Oslo, Oslo, Norway

[6] Oslo Univ Hosp, Rikshosp, Sect Clin Immunol & Infect Dis, Oslo, Norway

[7] Univ Oslo, KG Jebsen Inflammat Res Ctr, Oslo, Norway

[8] Univ Tromso, KG Jebsen Thrombosis Res & Expertise Ctr, Tromso, Norway

[9] Oslo Univ Hosp, Rikshosp, Dept Cardiothorac Surg, Oslo, Norway

[10] Oslo Univ Hosp, Rikshosp, Dept Cardiol, Oslo, Norway

[11] Norwegian Univ Sci & Technol, NTNU, Fac Med, Dept Circulat & Imaging, Trondheim, Norway

来源：

SCIENTIFIC REPORTS | 2017年 / 7卷

关键词：

FRIZZLED-RELATED PROTEINS; MUSCLE-CELL PROLIFERATION; HEART-FAILURE; PULMONARY-HYPERTENSION; EUROPEAN-ASSOCIATION; DOWN-REGULATION; EXPRESSION; DIFFERENTIATION; HYPERTROPHY; PATHWAY;

D O I：

10.1038/s41598-017-03625-9

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

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页数：10

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