{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T20:49:28Z","timestamp":1791146968977,"version":"4.1.0"},"reference-count":37,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2013,12,1]],"date-time":"2013-12-01T00:00:00Z","timestamp":1385856000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The pressure-loaded right ventricle (RV) adversely affects left ventricular (LV) function. We recently found that these ventricular\u2013ventricular interactions lead to LV myocardial fibrosis through transforming growth factor\u2013\u03b21 (TGF-\u03b21) signaling. We investigated the mechanisms mediating biventricular fibrosis in RV afterload and their potential modification by angiotensin receptor blockade. An adjustable pulmonary artery band (PAB) was placed in rabbits. In sham-operated control rabbits, the band was left uninflated (n = 6). In the RV afterload group, the PAB was sequentially inflated to generate systemic RV pressure at 28 days (n = 8). In a third group, the PAB was inflated to systemic levels, and the angiotensin receptor blocker losartan was added (n = 6). Five weeks after surgery, the animals were killed for assessments of biventricular hypertrophy, fibrosis, apoptosis, and the components of their signaling pathways. PAB animals developed biventricular hypertrophy, fibrosis, and apoptosis, versus sham rabbits, in which these conditions were decreased with losartan. RV and LV TGF-\u03b21, connective tissue growth factor (CTGF) (CCN2), endothelin-1 (ET-1), endothelin receptor B, and matrix metalloproteinase 2\/9 mRNA levels were increased in PAB animals versus sham animals, and decreased with losartan. Given the marked biventricular CTGF up-regulation in PAB and down-regulation with losartan, we investigated CTGF signaling. RV and LV Smad 2\/3\/4 protein levels and LV RhoA mRNA levels were increased with PAB and reduced with losartan. In conclusion, isolated RV afterload induces biventricular fibrosis and apoptosis, which are reduced by angiotensin receptor blockade. Adverse ventricular\u2013ventricular interactions induced by isolated RV afterload appear to be mediated through TGF-\u03b21\u2013CTGF and ET-1 pathways.<\/jats:p>","DOI":"10.1165\/rcmb.2013-0149oc","type":"journal-article","created":{"date-parts":[[2013,7,10]],"date-time":"2013-07-10T16:51:10Z","timestamp":1373475070000},"page":"1019-1028","source":"Crossref","is-referenced-by-count":82,"title":["Adverse Biventricular Remodeling in Isolated Right Ventricular Hypertension Is Mediated by Increased Transforming Growth Factor\u2013\u03b21 Signaling and Is Abrogated by Angiotensin Receptor Blockade"],"prefix":"10.1093","volume":"49","author":[{"given":"Mark K.","family":"Friedberg","sequence":"first","affiliation":[{"name":"Division of Cardiology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mi-Young","family":"Cho","sequence":"additional","affiliation":[{"name":"Division of Cardiology, 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