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Triiodothyronine maintains cardiac transverse-tubule structure and function.
Gilani, Nimra; Wang, Kaihao; Muncan, Adam; Peter, Jerrin; An, Shimin; Bhatti, Simran; Pandya, Khushbu; Zhang, Youhua; Tang, Yi-Da; Gerdes, A Martin; Stout, Randy F; Ojamaa, Kaie.
Afiliação
  • Gilani N; Department of Biomedical Sciences, New York Institute of Technology College of Osteopathic Medicine, Northern Blvd., Old Westbury, New York 11568, USA. Electronic address: ngilani@nyit.edu.
  • Wang K; Department of Biomedical Sciences, New York Institute of Technology College of Osteopathic Medicine, Northern Blvd., Old Westbury, New York 11568, USA; Department of Cardiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medic
  • Muncan A; Department of Biomedical Sciences, New York Institute of Technology College of Osteopathic Medicine, Northern Blvd., Old Westbury, New York 11568, USA. Electronic address: amuncan@nyit.edu.
  • Peter J; Department of Biomedical Sciences, New York Institute of Technology College of Osteopathic Medicine, Northern Blvd., Old Westbury, New York 11568, USA. Electronic address: jpeter@nyit.edu.
  • An S; Department of Biomedical Sciences, New York Institute of Technology College of Osteopathic Medicine, Northern Blvd., Old Westbury, New York 11568, USA; Department of Cardiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medic
  • Bhatti S; Department of Biomedical Sciences, New York Institute of Technology College of Osteopathic Medicine, Northern Blvd., Old Westbury, New York 11568, USA. Electronic address: sbhatt12@nyit.edu.
  • Pandya K; Department of Biomedical Sciences, New York Institute of Technology College of Osteopathic Medicine, Northern Blvd., Old Westbury, New York 11568, USA. Electronic address: kpandy04@nyit.edu.
  • Zhang Y; Department of Biomedical Sciences, New York Institute of Technology College of Osteopathic Medicine, Northern Blvd., Old Westbury, New York 11568, USA. Electronic address: yzhang49@nyit.edu.
  • Tang YD; Department of Cardiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China.
  • Gerdes AM; Department of Biomedical Sciences, New York Institute of Technology College of Osteopathic Medicine, Northern Blvd., Old Westbury, New York 11568, USA. Electronic address: martin.gerdes@nyit.edu.
  • Stout RF; Department of Biomedical Sciences, New York Institute of Technology College of Osteopathic Medicine, Northern Blvd., Old Westbury, New York 11568, USA; NYIT Imaging Center, New York Institute of Technology College of Osteopathic Medicine, Northern Blvd., Old Westbury, New York 11568, USA. Electronic
  • Ojamaa K; Department of Biomedical Sciences, New York Institute of Technology College of Osteopathic Medicine, Northern Blvd., Old Westbury, New York 11568, USA. Electronic address: kojamaa@nyit.edu.
J Mol Cell Cardiol ; 160: 1-14, 2021 11.
Article em En | MEDLINE | ID: mdl-34175303
ABSTRACT
Subclinical hypothyroidism and low T3 syndrome are commonly associated with an increased risk of cardiovascular disease (CVD) and mortality. We examined effects of T3 on T-tubule (TT) structures, Ca2+ mobilization and contractility, and clustering of dyadic proteins. Thyroid hormone (TH) deficiency was induced in adult female rats by propyl-thiouracil (PTU; 0.025%) treatment for 8 weeks. Rats were then randomized to continued PTU or triiodo-L-thyronine (T3; 10 µg/kg/d) treatment for 2 weeks (PTU + T3). After in vivo echocardiographic and hemodynamic recordings, cardiomyocytes (CM) were isolated to record Ca2+ transients and contractility. TT organization was assessed by confocal microscopy, and STORM images were captured to measure ryanodine receptor (RyR2) cluster number and size, and L-type Ca2+ channel (LTCC, Cav1.2) co-localization. Expressed genes including two integral TT proteins, junctophilin-2 (Jph-2) and bridging integrator-1 (BIN1), were analyzed in left ventricular (LV) tissues and cultured CM using qPCR and RNA sequencing. The T3 dosage used normalized serum T3, and reversed adverse effects of TH deficiency on in vivo measures of cardiac function. Recordings of isolated CM indicated that T3 increased rates of Ca2+ release and re-uptake, resulting in increased velocities of sarcomere shortening and re-lengthening. TT periodicity was significantly decreased, with reduced transverse tubules but increased longitudinal tubules in TH-deficient CMs and LV tissue, and these structures were normalized by T3 treatment. Analysis of STORM data of PTU myocytes showed decreased RyR2 cluster numbers and RyR localizations within each cluster without significant changes in Cav1.2 localizations within RyR clusters. T3 treatment normalized RyR2 cluster size and number. qPCR and RNAseq analyses of LV and cultured CM showed that Jph2 expression was T3-responsive, and its increase with treatment may explain improved TT organization and RyR-LTCC coupling.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Tri-Iodotironina / Sinalização do Cálcio / Ventrículos do Coração / Hipotireoidismo Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: J Mol Cell Cardiol Ano de publicação: 2021 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Tri-Iodotironina / Sinalização do Cálcio / Ventrículos do Coração / Hipotireoidismo Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: J Mol Cell Cardiol Ano de publicação: 2021 Tipo de documento: Article