title: Partially silencing brain toll-like receptor 4 prevents in part left ventricular remodeling with sympathoinhibition in rats with myocardial infarction-induced heart failure.
abstract: 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.
  
  
  RESULTS
  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.
authors.affiliation: Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Science, Fukuoka, Japan.
authors.forename: Kiyohiro
authors.initials: K
authors.lastname: Ogawa
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Hirooka
authors.forename: Takuya
authors.initials: T
authors.lastname: Kishi
authors.forename: Tomomi
authors.initials: T
authors.lastname: Ide
authors.forename: Kenji
authors.initials: K
authors.lastname: Sunagawa
mesh_terms: D000818:Animals; D001835:Body Weight; D001921:Brain / Q000378:metabolism*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D020868:Gene Silencing; D006333:Heart Failure / Q000209:etiology* / Q000503:physiopathology; D006439:Hemodynamics; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D009203:Myocardial Infarction / Q000150:complications* / Q000473:pathology / Q000503:physiopathology; D009929:Organ Size; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D051381:Rats; D013564:Sympathetic Nervous System / Q000502:physiology; D051197:Toll-Like Receptor 4 / Q000235:genetics* / Q000378:metabolism; D020257:Ventricular Remodeling / Q000235:genetics*
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D034741:RNA, Small Interfering; D051197:Toll-Like Receptor 4