Research Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
Faculty of Medicine, University of Oslo, Oslo, Norway.
Sci Rep. 2017 Jun 14;7(1):3490. doi: 10.1038/s41598-017-03625-9.
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.
无翅型（Wnt）信号通路与扩张型心肌病（DCM）的发病机制有关。为了探讨 Wnt 调节剂 Wnt5a 和 sFRP3 在 DCM 患者中的作用，我们分析了 DCM 患者血浆和心肌中 Wnt5a 和 sFRP3 的表达，并评估了它们对新生鼠心肌细胞 NFAT 荧光素酶活性的影响。循环 Wnt5a 升高（n=102）与肺动脉压升高、右心室功能下降和不良预后相关，在病情较重的患者中相关性更强。在右心室与左心室相比，发现 Wnt5a/sFRP3 比值更高（n=25），与 NFAT 激活和肺动脉压相关。Wnt5a 在体外诱导 NFAT 激活和 sFRP3 在心肌细胞中的释放，而 sFRP3 拮抗 Wnt5a。Wnt5a 与 DCM 患者的右心室功能障碍和不良预后相关，可能通过 NFAT 信号通路促进 DCM 的进展。
