ArticleMolecular medicine (Cambridge, Mass.)2019
Adverse transverse-tubule remodeling in a rat model of heart failure is attenuated with low-dose triiodothyronine treatment.
Article in Molecular medicine (Cambridge, Mass.), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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9 citing papers in PubMed, 16 citations in OpenAlex.
- Super-Resolution 3D Imaging Reveals Disarray of Dyadic Calcium Ion Channels in Failing Hearts Expressing Low Thyroid Hormone Function.International journal of molecular sciences · 2026Article
- Rethinking strategies for solving thyroid dysfunction at the heart of cardiovascular disease.Molecular medicine (Cambridge, Mass.) · 2025Review
- Excitation and mechanical contraction of a 3D cardiomyocyte model.Biophysical journal · 2025Article
- [Risk factors for cardiopulmonary dysfunction after ligation of hemodynamically significant patent ductus arteriosus in preterm infants].Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2025Article
- Cardiovascular Findings and Effects of Caffeine on Experimental Hypothyroidism.Endocrine, metabolic & immune disorders drug targets · 2025Article
- Thy and mighty: the importance of T3 thyroid hormone on dyadic structure and function in cardiac health and disease.American journal of physiology. Heart and circulatory physiology · 2024Article
- Nanoscale organization of cardiac calcium channels is dependent on thyroid hormone status.American journal of physiology. Heart and circulatory physiology · 2024Article
- Pirfenidone increases transverse tubule length in the infarcted rat myocardium.Interface focus · 2023Article
- Triiodothyronine maintains cardiac transverse-tubule structure and function.Journal of molecular and cellular cardiology · 2021Article
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8 authors at 2 institutions in 2 countries.
Funding
Abstract
Pre-clinical animal studies have shown that triiodothyronine (T3) replacement therapy improves cardiac contractile function after myocardial infarction (MI). We hypothesized that T3 treatment could prevent adverse post-infarction cardiomyocyte remodeling by maintaining transverse-tubule (TT) structures, thus improving calcium dynamics and contractility.
methodsMyocardial infarction (MI) or sham surgeries were performed on female Sprague-Dawley rats (aged 12 wks), followed by treatment with T3 (5μg/kg/d) or vehicle in drinking water for 16 wks (n = 10-11/group). After in vivo echocardiographic and hemodynamic analyses, left ventricular myocytes were isolated by collagenase digestion and simultaneous calcium and contractile transients in single cardiomyocytes were recorded using IonOptix imaging. Live cardiomyocytes were stained with AlexaFluor-488 conjugated wheat germ agglutinin (WGA-488) or di-8-ANEPPS, and multiple z-stack images per cell were captured by confocal microscopy for analysis of TT organization. RTqPCR and immunoblot approaches determined expression of TT proteins.
resultsEchocardiography and in vivo hemodynamic measurements showed significant improvements in systolic and diastolic function in T3- vs vehicle-treated MI rats. Isolated cardiomyocyte analysis showed significant dysfunction in measurements of myocyte relengthening in MI hearts, and improvements with T3 treatment: max relengthening velocity (Vmax, um/s), 2.984 ± 1.410 vs 1.593 ± 0.325, p < 0.05 and time to Vmax (sec), 0.233 ± 0.037 vs 0.314 ± 0.019, p < 0.001; MI + T3 vs MI + Veh, respectively. Time to peak contraction was shortened by T3 treatment (0.161 ± 0.021 vs 0.197 ± 0.011 s., p < 0.01; MI + T3 vs MI + Veh, respectively). Analysis of TT periodicity of WGA- or ANEPPS-stained cardiomyocytes indicated significant TT disorganization in MI myocytes and improvement with T3 treatment (transverse-oriented tubules (TE%): 9.07 ± 0.39 sham, 6.94 ± 0.67 MI + Veh and 8.99 ± 0.38 MI + T3; sham vs MI + Veh, p < 0.001; MI + Veh vs MI + T3, p < 0.01). Quantitative RT-PCR showed that reduced expression of BIN1 (Bridging integrator-1), Jph2 (junctophilin-2), RyR2 (ryanodine receptor) and Ca
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