Srxn1 Overexpression Protect Against Cardiac Remodelling by Inhibiting Oxidative Stress and Inflammation.

Abstract

Oxidative stress and inflammation are common medical issues contributing to the onset and progression of heart failure (HF). Sulfiredoxin 1 (Srxn1) is a key regulatory factor in the antioxidant response. This study aimed to examine the effect of Srxn1 in HF. We utilised transcriptome sequencing to screen for differentially expressed genes in cardiac remodelling. We overexpressed Srxn1 in the hearts using an adeno-associated virus 9 (AAV9) system through tail vein injection. C57BL/6 mice were subjected to transverse aortic constriction (TAC) for 4 weeks. Echocardiography was used to evaluate cardiac function, and cardiac remodelling was estimated by histopathology and molecular techniques. In addition, H9C2 cells were stimulated by Ang II to establish an in vitro model of cardiomyocyte hypertrophy, and the effects of Srxn1 overexpression on the inflammatory pathways and oxidative stress in Ang II-stimulated H9C2 cells were examined. We found that Srxn1 is downregulated after cardiac remodelling by transcriptome sequencing. Our results revealed down-regulated levels of Srxn1 in murine hearts subjected to TAC treatment, and H9C2 challenged with Ang II. Moreover, compared with WT mice, AAV-9-Srxn1 mice exhibited dramatically ameliorated TAC-induced cardiac dysfunction, hypertrophy, fibrosis, oxidative stress, and inflammation. In terms of mechanism, both in vitro and in vivo experiments confirmed that the potential positive impacts may be linked to the inhibition of TLR4/NF-κB signalling. In summary, this study is the first to demonstrate the protective effects of Srxn1 against TAC-induced cardiac oxidative stress and inflammation, which are induced by the inhibited activation of the TLR4/NF-κB signalling pathway.