The role of desmin alterations in mechanical electrical feedback in heart failure

Abstract

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, IKKβ, p-IKKβ, IKBα, p-NF-κB, 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-κB pathway, decrease the level of SERCA2, and result in abnormal distribution of Ca²⁺. While treatment with NF-κB inhibitor can elevate the level of SERCA2 and alleviate the abnormal distribution of Ca²⁺.

Significance: Overall, desmin may participate in MEF through the NF-κB pathway. This study provides a potential therapeutic target for VA in HF.

Keywords: Calpain-1; Desmin; HF; MEF; NF-κB; SERCA2; VA.