Research Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
Faculty of Medicine, University of Oslo, Oslo, Norway.
J Cardiovasc Transl Res. 2017 Aug;10(4):401-410. doi: 10.1007/s12265-017-9748-y. Epub 2017 May 4.
In dilated cardiomyopathy (DCM), adverse myocardial remodeling is essential, potentially involving Notch signaling. We hypothesized that secreted Notch ligands would be dysregulated in DCM. We measured plasma levels of the canonical Delta-like Notch ligand 1 (DLL1) and non-canonical Notch ligands Delta-like 1 homologue (DLK1) and periostin (POSN) in 102 DCM patients and 32 matched controls. Myocardial mRNA and protein levels of DLL1, DLK1, and POSN were measured in 25 explanted hearts. Our main findings were: (i) Circulating levels of DLL1 and POSN were higher in patients with severe DCM and correlated with the degree of diastolic dysfunction and (ii) right ventricular tissue expressions of DLL1, DLK1, and POSN were oppositely associated with cardiac function indices, as high DLL1 and DLK1 expression corresponded to more preserved and high POSN expression to more deteriorated cardiac function. DLL1, DLK1, and POSN are dysregulated in end-stage DCM, possibly mediating different effects on cardiac function.
在扩张型心肌病（DCM）中，不良的心肌重构是必不可少的，可能涉及 Notch 信号通路。我们假设分泌型 Notch 配体在 DCM 中会失调。我们测量了 102 例 DCM 患者和 32 例匹配对照者的血浆中典型的 Delta 样 Notch 配体 1（DLL1）和非典型 Notch 配体 Delta 样 1 同源物（DLK1）和骨粘连蛋白（POSN）的水平。我们还在 25 例心脏移植中测量了 DLL1、DLK1 和 POSN 的心肌 mRNA 和蛋白水平。我们的主要发现是：（i）严重 DCM 患者的循环 DLL1 和 POSN 水平较高，与舒张功能障碍的严重程度相关；（ii）右心室组织中 DLL1、DLK1 和 POSN 的表达与心功能指数呈相反关系，即高 DLL1 和 DLK1 表达对应于更保存的和高 POSN 表达对应于更恶化的心功能。DLL1、DLK1 和 POSN 在终末期 DCM 中失调，可能对心功能产生不同的影响。
