{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T12:57:47Z","timestamp":1762865867093},"reference-count":47,"publisher":"American Physiological Society","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"published-print":{"date-parts":[[2011,11]]},"abstract":"<jats:p>Li Y, Zhang H, Liao W, Song Y, Ma X, Chen C, Lu Z, Li Z, Zhang Y. \u03b1<jats:sub>1<\/jats:sub>-Adrenergic receptor (\u03b1<jats:sub>1<\/jats:sub>-AR) is a crucial mediator of cardiac hypertrophy. Although numerous intracellular pathways have been implicated in \u03b1<jats:sub>1<\/jats:sub>-AR-induced hypertrophy, its precise mechanism remains elusive. We aimed to determine whether \u03b1<jats:sub>1<\/jats:sub>-AR induces cardiac hypertrophy through a novel signaling pathway-\u03b1<jats:sub>1<\/jats:sub>-AR\/epidermal growth factor receptor (EGFR)\/signal transducer and activator of transcription 3 (STAT3). The activation of STAT3 by \u03b1<jats:sub>1<\/jats:sub>-AR was first demonstrated by tyrosine phosphorylation, nuclear translocation, DNA binding, and transcriptional activity in neonatal Sprague-Dawley rat cardiomyocytes. Activated STAT3 showed an essential role in \u03b1<jats:sub>1<\/jats:sub>-AR-induced cardiomyocyte hypertrophic growth, as assessed by treatment with STAT3 inhibitory peptide and lentivirus-STAT3 small interfering RNA. The results were further confirmed by in vivo experiments involving intraperitoneal injection of the STAT3 inhibitor WP1066 significantly inhibiting phenylephrine-infusion-induced heart hypertrophy in male C57BL\/6 mice. Furthermore, the \u03b1<jats:sub>1<\/jats:sub>-AR-activated STAT3 was associated with transactivation of EGFR because inhibition of EGFR with the selective inhibitor AG1478 prevented \u03b1<jats:sub>1<\/jats:sub>-AR-induced STAT3 tyrosine phosphorylation and its transcriptional activity, as well as cardiac hypertrophy. In summary, these results suggest that \u03b1<jats:sub>1<\/jats:sub>-AR induces the activation of STAT3, mainly through transactivation of EGFR, which plays an important role in \u03b1<jats:sub>1<\/jats:sub>-AR-induced cardiac hypertrophy.<\/jats:p>","DOI":"10.1152\/ajpheart.00338.2011","type":"journal-article","created":{"date-parts":[[2011,8,22]],"date-time":"2011-08-22T21:44:32Z","timestamp":1314049472000},"page":"H1941-H1951","source":"Crossref","is-referenced-by-count":28,"title":["Transactivated EGFR mediates \u03b1<sub>1<\/sub>-AR-induced STAT3 activation and cardiac hypertrophy"],"prefix":"10.1152","volume":"301","author":[{"given":"Yan","family":"Li","sequence":"first","affiliation":[{"name":"Institute of Vascular Medicine, Peking University Third Hospital, Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptide, Ministry of Health, and Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Beijing, People's Republic of 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