論文 - 詳細
| RRC ID | 68721 |
|---|---|
| 著者 | Ogawa K, Hirooka Y, Kishi T, Ide T, Sunagawa K. |
| タイトル | Partially silencing brain toll-like receptor 4 prevents in part left ventricular remodeling with sympathoinhibition in rats with myocardial infarction-induced heart failure. |
| ジャーナル | PLoS One |
| 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. 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. |
| 巻・号 | 8(7) |
| ページ | e69053 |
| 公開日 | 2013-1-1 |
| DOI | 10.1371/journal.pone.0069053 |
| PII | PONE-D-13-03071 |
| PMID | 23874864 |
| PMC | PMC3706428 |
| 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* |
| IF | 2.74 |
| リソース情報 | |
| ヒト・動物細胞 | C6(RCB2854) |