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Thyroid hormones regulate cardiac repolarization and QT-interval related gene expression in hiPSC cardiomyocytes.
Ulivieri, Alessandra; Lavra, Luca; Magi, Fiorenza; Morgante, Alessandra; Calò, Leonardo; Polisca, Patrizio; Salehi, Leila B; Sciacchitano, Salvatore.
Afiliação
  • Ulivieri A; Laboratory of Biomedical Research, Niccolò Cusano University Foundation, Via Don Carlo Gnocchi 3, 00166, Rome, Italy.
  • Lavra L; Laboratory of Biomedical Research, Niccolò Cusano University Foundation, Via Don Carlo Gnocchi 3, 00166, Rome, Italy.
  • Magi F; Laboratory of Biomedical Research, Niccolò Cusano University Foundation, Via Don Carlo Gnocchi 3, 00166, Rome, Italy.
  • Morgante A; Laboratory of Biomedical Research, Niccolò Cusano University Foundation, Via Don Carlo Gnocchi 3, 00166, Rome, Italy.
  • Calò L; Department of Cardiology, Policlinico Casilino, Via Casilina, 1049, 00169, Rome, Italy.
  • Polisca P; Laboratory of Biomedical Research, Niccolò Cusano University Foundation, Via Don Carlo Gnocchi 3, 00166, Rome, Italy.
  • Salehi LB; Laboratory of Biomedical Research, Niccolò Cusano University Foundation, Via Don Carlo Gnocchi 3, 00166, Rome, Italy.
  • Sciacchitano S; Medical Genetics Units, PTV, Tor Vergata University Hospital, Via Montpellier, 1, 00133, Rome, Italy.
Sci Rep ; 12(1): 568, 2022 01 12.
Article em En | MEDLINE | ID: mdl-35022468
ABSTRACT
Prolongation of cardiac repolarization (QT interval) represents a dangerous and potentially life-threatening electrical event affecting the heart. Thyroid hormones (THs) are critical for cardiac development and heart function. However, little is known about THs influence on ventricular repolarization and controversial effects on QT prolongation are reported. Human iPSC-derived cardiomyocytes (hiPSC-CMs) and multielectrode array (MEA) systems were used to investigate the influence of 3,3',5-triiodo-L-Thyronine (T3) and 3,3',5,5'-tetraiodo-L-Thyronine (T4) on corrected Field Potential Duration (FPDc), the in vitro analog of QT interval, and on local extracellular Action Potential Duration (APD). Treatment with high THs doses induces a significant prolongation of both FPDc and APD, with the strongest increase reached after 24 h exposure. Preincubation with reverse T3 (rT3), a specific antagonist for nuclear TH receptor binding, significantly reduces T3 effects on FPDc, suggesting a TRs-mediated transcriptional mechanism. RNA-seq analysis showed significant deregulation in genes involved in cardiac repolarization pathways, including several QT-interval related genes. In conclusion, long-time administration of high THs doses induces FPDc prolongation in hiPSC-CMs probably through the modulation of genes linked to QT-interval regulation. These results open the way to investigate new potential diagnostic biomarkers and specific targeted therapies for cardiac repolarization dysfunctions.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Hormônios Tireóideos / Síndrome do QT Longo / Regulação da Expressão Gênica / Miócitos Cardíacos Limite: Adolescent / Female / Humans Idioma: En Revista: Sci Rep Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Itália

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Hormônios Tireóideos / Síndrome do QT Longo / Regulação da Expressão Gênica / Miócitos Cardíacos Limite: Adolescent / Female / Humans Idioma: En Revista: Sci Rep Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Itália