{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T15:23:41Z","timestamp":1759332221819},"reference-count":56,"publisher":"American Physiological Society","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"published-print":{"date-parts":[[2011,10]]},"abstract":"<jats:p>In isolated myocytes, hypertrophy induced by norepinephrine is mediated via \u03b1<jats:sub>1<\/jats:sub>-adrenergic receptors (ARs) and not \u03b2-ARs. However, mice with deletions of both major cardiac \u03b1<jats:sub>1<\/jats:sub>-ARs still develop hypertrophy in response to pressure overload. Our purpose was to better define the role of \u03b2-AR subtypes in regulating cardiac hypertrophy in vivo, important given the widespread clinical use of \u03b2-AR antagonists and the likelihood that patients treated with these agents could develop conditions of further afterload stress. Mice with deletions of \u03b2<jats:sub>1<\/jats:sub>, \u03b2<jats:sub>2<\/jats:sub>, or both \u03b2<jats:sub>1<\/jats:sub>- and \u03b2<jats:sub>2<\/jats:sub>-ARs were subjected to transverse aortic constriction (TAC). After 3 wk, \u03b2<jats:sub>1<\/jats:sub><jats:sup>\u2212\/\u2212<\/jats:sup>showed a 21% increase in heart to body weight vs. sham controls, similar to wild type, whereas \u03b2<jats:sub>2<\/jats:sub><jats:sup>\u2212\/\u2212<\/jats:sup>developed exaggerated (49% increase) hypertrophy. Only when both \u03b2-ARs were ablated (\u03b2<jats:sub>1<\/jats:sub>\u03b2<jats:sub>2<\/jats:sub><jats:sup>\u2212\/\u2212<\/jats:sup>) was hypertrophy totally abolished. Cardiac function was preserved in all genotypes. Several known inhibitors of cardiac hypertrophy (FK506 binding protein 5, thioredoxin interacting protein, and S100A9) were upregulated in \u03b2<jats:sub>1<\/jats:sub>\u03b2<jats:sub>2<\/jats:sub><jats:sup>\u2212\/\u2212<\/jats:sup>compared with the other genotypes, whereas transforming growth factor-\u03b2<jats:sub>2<\/jats:sub>, a positive mediator of hypertrophy was upregulated in all genotypes except the \u03b2<jats:sub>1<\/jats:sub>\u03b2<jats:sub>2<\/jats:sub><jats:sup>\u2212\/\u2212<\/jats:sup>. In contrast to recent reports suggesting that angiogenesis plays a critical role in regulating cardiac hypertrophy-induced heart failure, we found no evidence that angiogenesis or its regulators (VEGF, Hif1\u03b1, and p53) play a role in compensated cardiac hypertrophy. Pressure overload hypertrophy in vivo is dependent on a coordination of signaling through both \u03b2<jats:sub>1<\/jats:sub>- and \u03b2<jats:sub>2<\/jats:sub>-ARs, mediated through several key cardiac remodeling pathways. Angiogenesis is not a prerequisite for compensated cardiac hypertrophy.<\/jats:p>","DOI":"10.1152\/ajpheart.00453.2010","type":"journal-article","created":{"date-parts":[[2011,6,25]],"date-time":"2011-06-25T05:31:42Z","timestamp":1308979902000},"page":"H1461-H1470","source":"Crossref","is-referenced-by-count":35,"title":["Cardiac pressure overload hypertrophy is differentially regulated by \u03b2-adrenergic receptor subtypes"],"prefix":"10.1152","volume":"301","author":[{"given":"Mingming","family":"Zhao","sequence":"first","affiliation":[{"name":"Departments of 1Pediatrics,"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giovanni","family":"Fajardo","sequence":"additional","affiliation":[{"name":"Departments of 1Pediatrics,"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takashi","family":"Urashima","sequence":"additional","affiliation":[{"name":"Departments of 1Pediatrics,"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joshua 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