AIM Dilated cardiomyopathy (DCM) is characterised by left ventricular dilation and associated with systolic dysfunction. Recent evidence has reported the high expression of latent transforming growth factor beta binding protein 2 (LTBP2) in heart diseases, which may play a role in regulating multiple biological functions of myocardial cells. Thus, this study set out to investigate the molecular mechanism and effects of LTBP2 in myocardial oxidative stress injury, fibrosis and remodelling in a rat model of DCM, with the involvement of NF-κB signalling pathway. METHODS The rat model of DCM was treated with si-LTBP2 and/or activator of NF-κB signalling pathway to examine the haemodynamic indexes, cardiac functions, oxidative stress injury, fibrosis and remodelling. Moreover, in vitro experiments were conducted to verify the regulatory role of LTBP2 and NF-κB signalling pathway in DCM. RESULTS LTBP2 was up-regulated in DCM rats. After LTBP2 was knocked down, haemodynamic indexes, HW/BW ratio, collagen volume fraction (CVF) level, positive expression of LTBP2, levels of reactive oxygen species (ROS), malondialdehyde (MDA), interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-α), tumour necrosis factor beta 1 (TGF-β1) and brain natriuretic peptide (BNP) were all decreased. Meanwhile, levels of LTBP2, Col-I, Col-III, p65 and p52 were also reduced, while HW, BW and levels of SOD and TAOC were increased. In contrast, activation of NF-κB signalling pathway reversed effects of LTBP2 gene silencing. These findings were confirmed by in vivo experiments. CONCLUSIONS LTBP2 silencing can attenuate myocardial oxidative stress injury, myocardial fibrosis and myocardial remodelling in DCM rats by down-regulating the NF-κB signalling pathway.

中文翻译：

---

siRNA对LTBP2的抑制作用可逆转扩张型心肌病期间的心肌氧化应激损伤，纤维化和重塑。

AIM扩张型心肌病（DCM）的特征在于左心室扩张，并伴有收缩功能障碍。最近的证据报道了潜在的转化生长因子β结合蛋白2（LTBP2）在心脏病中的高表达，这可能在调节心肌细胞的多种生物学功能中起作用。因此，本研究着手研究LTBP2在DCM大鼠模型中心肌氧化应激，纤维化和重塑中的分子机制及其作用，并涉及NF-κB信号通路。方法用si-LTBP2和/或NF-κB信号通路激活剂处理DCM大鼠模型，检查其血流动力学指标，心脏功能，氧化应激损伤，纤维化和重塑。而且，进行了体外实验，以验证LTBP2和NF-κB信号通路在DCM中的调节作用。结果LTBP2在DCM大鼠中上调。敲低LTBP2后，血流动力学指数，HW / BW比，胶原蛋白体积分数（CVF）水平，LTBP2阳性表达，活性氧（ROS），丙二醛（MDA），白介素6（IL-6），肿瘤坏死因子-α（TNF-α），肿瘤坏死因子-β1（TGF-β1）和脑利钠肽（BNP）均降低。同时，LTBP2，Col-I，Col-III，p65和p52的水平也降低，而HW，BW以及SOD和TAOC的水平升高。相反，NF-κB信号通路的激活逆转了LTBP2基因沉默的作用。这些发现通过体内实验得到了证实。