{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T07:27:55Z","timestamp":1790666875467,"version":"4.1.0"},"reference-count":45,"publisher":"American Physiological Society","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"published-print":{"date-parts":[[2013,9,15]]},"abstract":"<jats:p>In the present study, we compared the cardioprotective effects of TRV120023, a novel angiotensin II (ANG II) type 1 receptor (AT<jats:sub>1<\/jats:sub>R) ligand, which blocks G protein coupling but stimulates \u03b2-arrestin signaling, against treatment with losartan, a conventional AT<jats:sub>1<\/jats:sub>R blocker in the treatment of cardiac hypertrophy and regulation of myofilament activity and phosphorylation. Rats were subjected to 3 wk of treatment with saline, ANG II, ANG II + losartan, ANG II + TRV120023, or TRV120023 alone. ANG II induced increased left ventricular mass compared with rats that received ANG II + losartan or ANG II + TRV120023. Compared with saline controls, ANG II induced a significant increase in pCa<jats:sub>50<\/jats:sub>and maximum Ca<jats:sup>2+<\/jats:sup>-activated myofilament tension but reduced the Hill coefficient ( n<jats:sub>H<\/jats:sub>). TRV120023 increased maximum tension and pCa<jats:sub>50<\/jats:sub>, although to lesser extent than ANG II. In contrast to ANG II, TRV120023 increased n<jats:sub>H<\/jats:sub>. Losartan blocked the effects of ANG II on pCa<jats:sub>50<\/jats:sub>and n<jats:sub>H<\/jats:sub>and reduced maximum tension below that of saline controls. ANG II + TRV120023 showed responses similar to those of TRV120023 alone; compared with ANG II + losartan, ANG II + TRV120023 preserved maximum tension and increased both pCa<jats:sub>50<\/jats:sub>and cooperativity. Tropomyosin phosphorylation was lower in myofilaments from saline-treated hearts compared with the other groups. Phosphorylation of cardiac troponin I was significantly reduced in ANG II + TRV120023 and TRV120023 groups versus saline controls, and myosin-binding protein C phosphorylation at Ser<jats:sup>282<\/jats:sup>was unaffected by ANG II or losartan but significantly reduced with TRV120023 treatment compared with all other groups. Our data indicate that TRV120023-related promotion of \u03b2-arrestin signaling and enhanced contractility involves a mechanism promoting the myofilament response to Ca<jats:sup>2+<\/jats:sup>via altered protein phosphorylation. Selective activation of \u03b2-arrestin-dependent pathways may provide advantages over conventional AT<jats:sub>1<\/jats:sub>R blockers.<\/jats:p>","DOI":"10.1152\/ajpheart.00327.2013","type":"journal-article","created":{"date-parts":[[2013,7,20]],"date-time":"2013-07-20T05:08:31Z","timestamp":1374296911000},"page":"H856-H866","source":"Crossref","is-referenced-by-count":73,"title":["The \u03b2-arrestin-biased ligand TRV120023 inhibits angiotensin II-induced cardiac hypertrophy while preserving enhanced myofilament response to calcium"],"prefix":"10.1152","volume":"305","author":[{"given":"Michelle M.","family":"Monasky","sequence":"first","affiliation":[{"name":"Department of Physiology and Biophysics and Center for Cardiovascular Research, College of Medicine, University of Illinois, Chicago, Illinois; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Domenico M.","family":"Taglieri","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics and Center for Cardiovascular Research, College of Medicine, University of Illinois, Chicago, Illinois; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus","family":"Henze","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics and Center for Cardiovascular Research, College of Medicine, University of Illinois, Chicago, Illinois; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chad M.","family":"Warren","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics and Center for Cardiovascular Research, College of Medicine, University of Illinois, Chicago, Illinois; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan S.","family":"Utter","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics and Center for Cardiovascular Research, College of Medicine, University of Illinois, Chicago, Illinois; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David G.","family":"Soergel","sequence":"additional","affiliation":[{"name":"Trevena Incorporated, King of Prussia, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan D.","family":"Violin","sequence":"additional","affiliation":[{"name":"Trevena Incorporated, King of Prussia, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. 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