Reference - Detail
|Author||Ogawa K, Hirooka Y, Kishi T, Ide T, Sunagawa K.|
|Title||Partially silencing brain toll-like receptor 4 prevents in part left ventricular remodeling with sympathoinhibition in rats with myocardial infarction-induced heart failure.|
BACKGROUND:Left ventricular (LV) remodeling and activation of sympathetic nervous system (SNS) are cardinal features of heart failure. We previously demonstrated that enhanced central sympathetic outflow is associated with brain toll-like receptor 4 (TLR4) probably mediated by brain angiotensin II type 1 receptor in mice with myocardial infarction (MI)-induced heart failure. The purpose of the present study was to examine whether silencing brain TLR4 could prevent LV remodeling with sympathoinhibition in MI-induced heart failure.
METHODOLOGY/PRINCIPAL FINDINGS:MI-induced heart failure model rats were created by ligation of left coronary artery. The expression level of TLR4 in brainstem was significantly higher in MI-induced heart failure treated with intracerebroventricular (ICV) injection of hGAPDH-SiRNA than in sham. TLR4 in brainstem was significantly lower in MI-induced heart failure treated with ICV injection of TLR4-SiRNA than in that treated with ICV injection of hGAPDH-SiRNA. Lung weight, urinary norepinephrine excretion, and LV end-diastolic pressure were significantly lower and LV dimension was significantly smaller in MI-induced heart failure treated with TLR4-SiRNA than in that treated with hGAPDH-SiRNA for 2 weeks.
CONCLUSIONS:Partially silencing brain TLR4 by ICV injection of TLR4-SiRNA for 2 weeks could in part prevent LV remodeling with sympathoinhibition in rats with MI-induced heart failure. Brain TLR4 has a potential to be a target of the treatment for MI-induced heart failure.
|MeSH||Animals Body Weight Brain / metabolism* Cytokines / genetics Cytokines / metabolism Gene Expression Regulation Gene Silencing* Heart Failure / etiology* Heart Failure / physiopathology Hemodynamics Inflammation Mediators / metabolism Male Myocardial Infarction / complications* Myocardial Infarction / pathology Myocardial Infarction / physiopathology Organ Size RNA Interference RNA, Small Interfering / genetics RNA, Small Interfering / metabolism Rats Sympathetic Nervous System* / physiology Toll-Like Receptor 4 / genetics* Toll-Like Receptor 4 / metabolism Ventricular Remodeling / genetics*|
|Human and Animal Cells||C6(RCB2854)|