Retracted: IRAK3 gene silencing prevents cardiac rupture and ventricular remodeling through negative regulation of the NF‐κB signaling pathway in a mouse model of acute myocardial infarction

Abstract

Cardiac rupture and ventricular remodeling are recognized as the severe complications and major risk factors of acute myocardial infarction (AMI). This study aims to evaluate the regulatory roles of interleukin‐1 receptor‐associated kinase 3 (IRAK3) and nuclear factor‐κB (NF‐κB) signaling pathway in cardiac rupture and ventricular remodeling. Microarray analysis was performed to screen AMI‐related differentially expressed genes and IRAK3 was identified. The models of AMI were established in male C57BL/6 mice to investigate the functional role of IRAK3. Afterwards, lentivirus recombinant plasmid si‐IRAK3 was constructed for IRAK3 silencing. Next, cardiac function parameters were measured in response to IRAK3 silencing. The regulatory effects that IRAK3 had on myocardial infarct size and the content of myocardial interstitial collagen were analyzed. The regulation of IRAK3 silencing on the NF‐κB signaling pathway was further assayed. The obtained results indicated that highly expressed IRAK3 and activated NF‐κB signaling pathway were observed in myocardial tissues of mouse models of AMI, accompanied by increased expression of matrix metalloproteinase (MMP)‐2/9 and tissue inhibitor of metalloproteinase 2 (TIMP‐2). Notably, IRAK3 gene silencing inhibited the activation of NF‐κB signaling pathway. Furthermore, IRAK3 gene silencing led to the decreased thickness of infarct area and collagen content of myocardial interstitium, alleviated diastolic, and systolic dysfunctions, as well as, facilitated cardiac functions in mice with AMI, corresponding to decreased expression of MMP‐2/9 expression and increased expression of TIMP‐2. Taken together, silencing of IRAK3 inactivates the NF‐κB signaling pathway, and thereby impeding the cardiac rupture and ventricular remodeling, which eventually prevents AMI progression.

Predicting Diagnostic Gene Biomarkers Associated With Immune Infiltration in Patients With Acute Myocardial Infarction

“…Interleukin 1 receptor associated kinase 3 (IRAK3), which encodes a member of the IL-1 receptor-associated kinase protein family, functions as a negative regulator of Toll-like receptor signaling and participates in innate host defense and in the control of adaptive immune responses (39). Evidence in a mouse model of AMI demonstrated that IRAK3 gene silencing could minimize AMI damage, indicated by a reduced infarct area and collagen content (40). A mutation in the thrombomodulin (THBD) gene is the main cause of thromboembolic disease.…”

Silencing of ATP2B1‐AS1 contributes to protection against myocardial infarction in mouse via blocking NFKBIA‐mediated NF‐κB signalling pathway

“…In addition, NF‐κB still exerts impacts on oxidative stress, genotoxic stress and the self‐regulation of homeostatic functions . Activated NF‐κB signalling pathway can be observed in myocardial tissues from AMI mouse model, while impaired NF‐κB signalling pathway could impede the cardiac rupture and ventricular remodelling . However, investigations on the roles of lncRNAs and NF‐κB and their interaction in MI are still limited.…”

Matrix Metalloproteinases and Their Role in Mechanisms Underlying Effects of Quercetin on Heart Function in Aged Zucker Diabetic Fatty Rats

“…This enzyme is the newest identified member of the MMP family and it has been documented that MMP-28 protein levels decrease in response to pathological conditions [ 45 ]. In contrast to MMP-2 and MMP-9 where myocardial infarction (MI) induced increase of their levels/activities [ 46 , 47 ], MMP-28 levels decreased post-MI [ 45 ]. Moreover, deletion of MMP-28 increased dysfunction of the left ventricle post-MI by reduction of inflammatory and fibrotic responses.…”