Document Detail


Angiotensin II type 1 receptor expression in astrocytes is upregulated leading to increased mortality in mice with myocardial infarction-induced heart failure.
MedLine Citation:
PMID:  25217656     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Enhanced central sympathetic outflow worsens left ventricular (LV) remodeling and prognosis in heart failure after myocardial infarction (MI). Previous studies suggested that activation of brain angiotensin II type 1 receptors (AT1R) in the brainstem leads to sympathoexcitation due to neuronal AT1R upregulation. Recent studies, however, revealed the importance of astrocytes for modulating neuronal activity, but whether changes in astrocytes influence central sympathetic outflow in heart failure is unknown. In the normal state, AT1R are only weakly expressed in astrocytes. We hypothesized that AT1R in astrocytes are upregulated in heart failure, and modulate the activity of adjacent neurons, leading to enhanced sympathetic outflow. In the present study, by targeting deletion of astrocyte-specificAT1R, we investigated whetherAT1R in astrocytes have a key role in enhancing central sympathetic outflow, and thereby influencing LV remodeling process and the prognosis of MI-induced heart failure. Using the Cre-LoxP system, we generated glial fibrillary acidic protein (GFAP)-specific AT1R knockout (GFAP/AT1RKO) mice. Urinary norepinephrine excretion for 24 h, as an indicator of sympathoexcitation, was significantly lower in GFAP/AT1RKO-MI mice than in control-MI mice. LV size and heart weight after MI were significantly smaller in GFAP/AT1RKO mice than in control mice. Prognosis was significantly improved in GFAP/AT1RKO-MI mice compared to control-MI mice. Our findings indicated that AT1R expression was upregulated in brainstem astrocytes in MI-induced heart failure, which worsened LV remodeling and prognosis via sympathoexcitation. Thus, in addition to neuronal AT1R, AT1R in astrocytes appear to have a key role in enhancing central sympathetic outflow in heart failure.
Authors:
Kengo Isegawa; Yoshitaka Hirooka; Masato Katsuki; Takuya Kishi; Kenji Sunagawa
Related Documents :
20703546 - Evaluation of a novel integrated sensor system for synchronous measurement of cardiac v...
21242796 - Improvements of cardiac electrophysiologic stability and ventricular fibrillation thres...
22197106 - Very late stent thrombosis immediately after recurrent inappropriate shock delivery by ...
20587506 - Cardiac electrophysiological effects of nitric oxide.
6433826 - Electrical alternans. an association with coronary artery spasm.
23261676 - (-) epicatechin attenuates mitochondrial damage by enhancing mitochondrial multi-marker...
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-9-12
Journal Detail:
Title:  American journal of physiology. Heart and circulatory physiology     Volume:  -     ISSN:  1522-1539     ISO Abbreviation:  Am. J. Physiol. Heart Circ. Physiol.     Publication Date:  2014 Sep 
Date Detail:
Created Date:  2014-9-13     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100901228     Medline TA:  Am J Physiol Heart Circ Physiol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2014, American Journal of Physiology - Heart and Circulatory Physiology.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  The Tell-Tale Heart: Molecular and Cellular Responses to Childhood Anthracycline Exposure.
Next Document:  Hematocrit dispersion in asymmetrically bifurcating vascular networks.