The role of desmin alterations in mechanical electrical feedback in heart failure
The role of desmin alterations in mechanical electrical feedback in heart failure
复制标题
结蛋白改变在心力衰竭机械电反馈中的作用
DOI：
10.1016/j.lfs.2019.117119
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发表时间：
2020-01-15
期刊：
影响因子：
6.1
通讯作者：
Fu, Lu
中科院分区：
文献类型：
--
作者：
Chen, Lin;Wang, Li;Fu, Lu
目的：机电反馈（MEF）与心力衰竭（HF）患者恶性心律失常的关系。Desmin是一种细胞骨架蛋白，可作为机电换能器参与MEF。在这项研究中，我们将讨论desmin改变在心力衰竭中机械电反馈的作用及其机制。方法：采用大鼠体内模型和体外心肌细胞模型来解决这一问题。在体内实验中，我们建立了假手术组、HF组、链霉素组和MDL-28170组。记录各组室性心律失常（VA）发生情况。体外心肌细胞模型建立NC组、si-desmin组和si-desmin + NBD IKK组。在体内和体外实验中检测desmin、IKK β、p-IKK β、IKB α、p- nf - κ B和SERCA2的表达。体外实验采用共聚焦成像技术检测细胞质和肌浆中Ca2+含量。结果：HF组VAs评分明显增加。SM和MDL-28170可降低心衰患者desmin衰竭及VAs数量。心肌细胞中desmin的下调可激活NF-kappa B通路，降低SERCA2水平，导致Ca2+分布异常。而nf - κ B抑制剂治疗可提高SERCA2水平，缓解Ca2+的异常分布。意义：总体而言，desmin可能通过NF-kappa B通路参与MEF。本研究为心衰患者提供了一个潜在的治疗靶点。
Aim: Mechanoelectric feedback (MEF) was related to malignant arrhythmias in heart failure (HF). Desmin is a cytoskeleton protein and could be involved in MEF as a mechanoelectrical transducer. In this study, we will discuss the role of desmin alterations in mechanical electrical feedback in heart failure and its mechanisms.Methods: We used both an in vivo rat model and an in vitro cardiomyocyte model to address this issue. For the in vivo experiments, we establish a sham group, an HF group, streptomycin (SM) group, and an MDL-28170 group. The occurrence of ventricular arrhythmias (VA) was recorded in each group. For the in vitro cardiomyocyte model, we established an NC group, a si-desmin group, and a si-desmin + NBD IKK group. The expression of desmin, IKK beta, p-IKK beta, IKB alpha, p-NF-kappa B, and SERCA2 were detected in both in vivo and in vitro experiments. The content of Ca2+ in cytoplasm and sarcoplasmic were detected by confocal imaging in vitro experiments.Results: An increased number of VAs were found in the HF group. SM and MDL-28170 can reduce desmin breakdown and the number of VAs in heart failure. The knockdown of desmin in the cardiomyocyte can activate the NF-kappa B pathway, decrease the level of SERCA2, and result in abnormal distribution of Ca2+. While treatment with NF-kappa B inhibitor can elevate the level of SERCA2 and alleviate the abnormal distribution of Ca2+.Significance: Overall, desmin may participate in MEF through the NF-kappa B pathway. This study provides a potential therapeutic target for VA in HF.