{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T09:31:19Z","timestamp":1768815079967,"version":"3.49.0"},"reference-count":51,"publisher":"American Physiological Society","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"published-print":{"date-parts":[[2014,11,15]]},"abstract":"<jats:p> 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 (AT<jats:sub>1<\/jats:sub>R) in the brain stem leads to sympathoexcitation due to neuronal AT<jats:sub>1<\/jats:sub>R 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, AT<jats:sub>1<\/jats:sub>R are only weakly expressed in astrocytes. We hypothesized that AT<jats:sub>1<\/jats:sub>R 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-specific AT<jats:sub>1<\/jats:sub>R, we investigated whether AT<jats:sub>1<\/jats:sub>R 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 AT<jats:sub>1<\/jats:sub>R knockout (GFAP\/AT<jats:sub>1<\/jats:sub>RKO) mice. Urinary norepinephrine excretion for 24 h, as an indicator of sympathoexcitation, was significantly lower in GFAP\/AT<jats:sub>1<\/jats:sub>RKO-MI mice than in control-MI mice. LV size and heart weight after MI were significantly smaller in GFAP\/AT<jats:sub>1<\/jats:sub>RKO mice than in control mice. Prognosis was significantly improved in GFAP\/AT<jats:sub>1<\/jats:sub>RKO-MI mice compared with control-MI mice. Our findings indicated that AT<jats:sub>1<\/jats:sub>R expression was upregulated in brain stem astrocytes in MI-induced heart failure, which worsened LV remodeling and prognosis via sympathoexcitation. Thus, in addition to neuronal AT<jats:sub>1<\/jats:sub>R, AT<jats:sub>1<\/jats:sub>R in astrocytes appear to have a key role in enhancing central sympathetic outflow in heart failure. <\/jats:p>","DOI":"10.1152\/ajpheart.00462.2014","type":"journal-article","created":{"date-parts":[[2014,9,12]],"date-time":"2014-09-12T23:47:17Z","timestamp":1410565637000},"page":"H1448-H1455","source":"Crossref","is-referenced-by-count":42,"title":["Angiotensin II type 1 receptor expression in astrocytes is upregulated leading to increased mortality in mice with myocardial infarction-induced heart failure"],"prefix":"10.1152","volume":"307","author":[{"given":"Kengo","family":"Isegawa","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshitaka","family":"Hirooka","sequence":"additional","affiliation":[{"name":"Department of Advanced 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