TLR4 participates in sympathetic hyperactivity Post-MI in the PVN by regulating NF-κB pathway and ROS production

Publication date: Available online 2 April 2019Source: Redox BiologyAuthor(s): Yu Wang, Hesheng Hu, Jie Yin, Yugen Shi, Jiayu Tan, Lu Zheng, Cailing Wang, Xiaolu Li, Mei Xue, Ju Liu, Ye Wang, Yan Li, Xinran Li, Fuhong Liu, Qiang Liu, Suhua YanAbstractSympathetic nerve hyperactivity is a primary reason for fatal ventricular arrhythmias (VAs) following myocardial infarction (MI). Pro-inflammatory cytokines produced in the paraventricular nucleus (PVN) post-MI are associated with sympathetic overexcitation; however, the precise mechanism needs further investigation. Our aim was to explore the mechanism of toll-like receptor 4 (TLR4) and its downstream molecular pathway in mediating sympathetic activity post-MI within the PVN. A rat MI model was developed via left anterior descending coronary artery ligation. TLR4 was primarily localized in microglia and increased markedly within the PVN at 3 days in MI rats. Sympathoexcitation also increased, as indicated by high levels of renal sympathetic nerve activity (RSNA) and norepinephrine (NE) concentration. TLR4 knockdown via shRNA microinjection to the PVN resulted in decreased activation of Fos protein (+) neurons in the PVN and peripheral sympathetic nerve activity. TLR4 knockdown also exhibited a lower arrhythmia score following programmed electrical stimulation than those treated with MI surgery only, indicating that the knockdown of TLR4 decreased the incidence of malignant ventricular arrhythmias following MI. LPS-induced inflam...
Source: Redox Biology - Category: Biology Source Type: research