{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T08:02:27Z","timestamp":1767168147411,"version":"build-2238731810"},"reference-count":40,"publisher":"American Physiological Society","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"published-print":{"date-parts":[[2009,8]]},"abstract":"<jats:p>Myotrophin-induced activation of NF-\u03baB has been shown to be associated with cardiac hypertrophy (CH) that progresses to heart failure (HF). In the present study, we examined the cause-and-effect relationship between myotrophin and NF-\u03baB activation using small hairpin RNA (shRNA) against myotrophin both in vitro (using neonatal rat myocytes) and in vivo [using myotrophin transgenic (Myo-Tg) mice, which overexpress myotrophin in the heart, develop CH, and gradually progress to HF]. Among several lentiviral vectors expressing myotrophin shRNAs, L-sh-109 showed the best silencing effect at both the mRNA (155.3 \u00b1 5.9 vs. 32.5 \u00b1 5.5, P &lt; 0.001) and protein levels associated with a significant reduction of atrial natriuretic factor (ANF) and NF-\u03baB. In vivo, when L-sh-109 was delivered directly into the hearts of 10-wk-old Myo-Tg mice, we observed a significant regression of cardiac mass (8.0 vs. 5.7 mg\/g, P &lt; 0.001) and myotrophin gene expression (54.5% over untreated Myo-Tg mice, P &lt; 0.001) associated with a reduction in ANF and NF-\u03baB signaling components. Our data suggest that using RNA interference to silence the myotrophin gene prevents NF-\u03baB activation, associated with an attenuation of CH. This strategy could be an excellent therapeutic means for the treatment of CH and HF.<\/jats:p>","DOI":"10.1152\/ajpheart.00294.2009","type":"journal-article","created":{"date-parts":[[2009,6,5]],"date-time":"2009-06-05T21:50:16Z","timestamp":1244238616000},"page":"H627-H636","source":"Crossref","is-referenced-by-count":11,"title":["Silencing the myotrophin gene by RNA interference leads to the regression of cardiac hypertrophy"],"prefix":"10.1152","volume":"297","author":[{"given":"Sudhiranjan","family":"Gupta","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ratan","family":"Maitra","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dave","family":"Young","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anasuya","family":"Gupta","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Subha","family":"Sen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","reference":[{"key":"R1","doi-asserted-by":"publisher","DOI":"10.1089\/104303402320987888"},{"key":"R2","doi-asserted-by":"publisher","DOI":"10.1038\/35053110"},{"key":"R3","doi-asserted-by":"publisher","DOI":"10.1126\/science.1068999"},{"key":"R4","doi-asserted-by":"crossref","unstructured":"Chen F\n                      , Castranova V, Shi X, Demers LMA.\n                      New insights into the role of nuclear factor-\u03baB, a ubiquitous transcription factor in the initiation of diseases.\n                      Clin Chem\n                      45\n                      : 7\u201317, 1999.","DOI":"10.1093\/clinchem\/45.1.7"},{"key":"R5","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.ph.55.030193.000453"},{"key":"R6","doi-asserted-by":"crossref","unstructured":"Chomczynski P\n                      , Sacchi N.\n                      Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction.\n                      Anal Biochem\n                      162\n                      : 156\u2013159, 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