{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T17:01:20Z","timestamp":1790096480172,"version":"4.0.1"},"reference-count":40,"publisher":"American Society for Clinical Investigation","issue":"18","license":[{"start":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:00:00Z","timestamp":1790035200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Key Special Science and Technology Project","award":["2025ZD0552203"],"award-info":[{"award-number":["2025ZD0552203"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,22]]},"abstract":"<jats:p>\n                    Right ventricular pressure overload (RVPO) is a critical pathophysiological feature of numerous pediatric cardiovascular diseases. Transverse tubules (T-tubules) form the foundation for efficient excitation-contraction coupling in mature cardiomyocytes. We hypothesized that RVPO impairs T-tubule maturation through the regulatory protein bridging integrator 1 (BIN1). In right ventricular samples from children with tetralogy of Fallot, characterized by RVPO, and in a neonatal rat RVPO model induced by pulmonary artery banding (PAB), T-tubule maturation was disrupted. RNA-seq revealed significant downregulation of T-tubule\u2013associated genes, with\n                    <jats:italic>Bin1<\/jats:italic>\n                    among the most suppressed.\n                    <jats:italic>Bin1<\/jats:italic>\n                    overexpression restored T-tubule maturation in PAB rats. ATAC-seq showed reduced chromatin accessibility at\n                    <jats:italic>Bin1<\/jats:italic>\n                    loci; motif analysis identified\n                    <jats:italic>Mef2d<\/jats:italic>\n                    (myocyte enhancer factor 2D) as the top enriched transcription factor.\n                    <jats:italic>Mef2d<\/jats:italic>\n                    knockdown rescued\n                    <jats:italic>Bin1<\/jats:italic>\n                    expression and T-tubule maturation, and mutation of the\n                    <jats:italic>Mef2d<\/jats:italic>\n                    binding sites within the\n                    <jats:italic>Bin1<\/jats:italic>\n                    promoter abolished the inhibitory effect of\n                    <jats:italic>Mef2d<\/jats:italic>\n                    on\n                    <jats:italic>Bin1<\/jats:italic>\n                    promoter activity. This study delineates a phenomenon and a mechanism of cardiomyocyte maturation under pathological stress. The findings not only advance our understanding of this most pivotal event in postnatal cardiac development but also unveil a potential therapeutic direction for pediatric cardiovascular diseases associated with RVPO.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.204032","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T18:01:08Z","timestamp":1790013668000},"source":"Crossref","is-referenced-by-count":0,"title":["Right ventricular pressure overload disturbs T-tubule maturation via MEF2D\u2019s transcriptional regulation of BIN1"],"prefix":"10.1172","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8845-7176","authenticated-orcid":true,"given":"Yuqing","family":"Hu","sequence":"first","affiliation":[{"name":"Department of Cardiology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiting","family":"Xue","sequence":"additional","affiliation":[{"name":"Department of Thoracic and Cardiovascular Surgery, 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