{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T23:32:40Z","timestamp":1788478360230,"version":"build-2803163510"},"reference-count":42,"publisher":"American Physiological Society","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"published-print":{"date-parts":[[2013,5,15]]},"abstract":"<jats:p>\n                    Pulmonary insufficiency (PI) is a common long-term sequel after repair of tetralogy of Fallot, causing progressive right ventricular (RV) dilation and failure. We describe the physiologic and molecular characteristics of the first murine model of RV volume overload. PI was created by entrapping the pulmonary valve leaflets with sutures. Imaging, catheterization, and exercise testing were performed at 1, 3, and 6 mo and compared with sham controls. RNA from the RV free wall was hybridized to Agilent whole genome oligonucleotide microarrays. Volume overload resulted in RV enlargement, decreased RV outflow tract shortening fraction at 1 mo followed by normalization at 3 and 6 mo (39 \u00b1 2, 44 \u00b1 2, and 41 \u00b1 2 vs. 46 \u00b1 3% in sham), early reversal of early and late diastolic filling velocities (E\/A ratio) followed by pseudonormalization (0.87 \u00b1 0.08, 0.82 \u00b1 0.08, and 0.96 \u00b1 0.08 vs. 1.04 \u00b1 0.03; P &lt; 0.05), elevated end-diastolic pressure (7.6 \u00b1 0.7, 6.9 \u00b1 0.8, and 7 \u00b1 0.5 vs. 2.7 \u00b1 0.2 mmHg; P &lt; 0.05), and decreased exercise duration (26 \u00b1 0.4, 26 \u00b1 1, and 22 \u00b1 1.3 vs. 30 \u00b1 1.1 min; P &lt; 0.05). Subendocardial RV fibrosis was evident by 1 mo. At 1 mo, 372 genes were significantly downregulated. Mitochondrial pathways and G protein-coupled receptor signaling were the most represented categories. At 3 mo, 434 genes were upregulated and 307 downregulated. While many of the same pathways continued to be downregulated, TNF-\u03b1, transforming growth factor-\u03b2\n                    <jats:sub>1<\/jats:sub>\n                    (TGF-\u03b2\n                    <jats:sub>1<\/jats:sub>\n                    ), p53-signaling, and extracellular matrix (ECM) remodeling transitioned from down- to upregulated. We describe a novel murine model of chronic RV volume overload recapitulating aspects of the clinical disease with gene expression changes suggesting early mitochondrial bioenergetic dysfunction, enhanced TGF-\u03b2 signaling, ECM remodeling, and apoptosis.\n                  <\/jats:p>","DOI":"10.1152\/ajpheart.00776.2012","type":"journal-article","created":{"date-parts":[[2013,3,16]],"date-time":"2013-03-16T03:37:02Z","timestamp":1363405022000},"page":"H1314-H1327","source":"Crossref","is-referenced-by-count":77,"title":["Physiologic and molecular characterization of a murine model of right ventricular volume overload"],"prefix":"10.1152","volume":"304","author":[{"given":"Sushma","family":"Reddy","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Stanford University School of Medicine, Stanford, California;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingming","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Stanford University School of Medicine, Stanford, California;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong-Qing","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Stanford University School of Medicine, Stanford, California;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Fajardo","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Stanford University School of Medicine, Stanford, California;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ethan","family":"Katznelson","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Stanford University School of Medicine, Stanford, California;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajesh","family":"Punn","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Stanford University School of Medicine, Stanford, California;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua M.","family":"Spin","sequence":"additional","affiliation":[{"name":"Department of Medicine, Stanford University School of Medicine, Stanford, California; 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