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Cited by 179Thyroid Disorders and TreatmentsCardiovascular Function and Risk FactorsCardiac Fibrosis and Remodeling

Low thyroid function leads to cardiac atrophy with chamber dilatation, impaired myocardial blood flow, loss of arterioles, and severe systolic dysfunction

Tang, Yi-Da, Kuzman, James A., Said, Suleman, Anderson, Brent E., Wang, Xuejun, Gerdes, A. Martin·2005·Circulation
DOI 10.1161/circulationaha.105.572883
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Abstract

Background— Although thyroid dysfunction has been linked to heart failure, it is not clear whether hypothyroidism alone can cause heart failure. Methods and Results— Hypothyroidism was induced in adult rats by treatment with 0.025% propylthiouracil (PTU) for 6 weeks (PTU-S) and 1 year (PTU-L). Echocardiographic measurements, left ventricular (LV) hemodynamics, isolated myocyte length (KOH method), myocardial blood flow (fluorescent microspheres), arteriolar morphometry, and gene expression (Western blot) were determined. Heart weight, heart rate, LV systolic blood pressure, LV ejection fraction, LV fractional shortening, and systolic wall thickness were reduced in PTU-S and PTU-L rats. LV internal diameter in systole increased by 40% in PTU-S and 86% in PTU-L. LV internal dimension in diastole was increased in PTU-S and PTU-L rats, but only PTU-L rats showed a significant increase in myocyte length due to series sarcomere addition. Resting and maximum (adenosine) myocardial blood flow were reduced in both PTU-S and PTU-L rats. Impaired blood flow was due to a large reduction in arteriolar length density and small arterioles in PTU-S and PTU-L ( P <0.05 or greater for all of the above comparisons). Expression of sarcoplasmic/endoplasmic reticulum Ca 2+ -ATPase (SERCA)-2a and α-myosin heavy chain were reduced in hypothyroidism, whereas phospholamban and β-myosin heavy chain were increased. Conclusions— Hypothyroidism led to severe, progressive systolic dysfunction and increased chamber diameter/wall thickness ratio despite a reduction in cardiac mass. Chamber dilatation in PTU-L rats was due to series sarcomere addition, typical of heart failure. Hypothyroidism resulted in impaired myocardial blood flow due to a dramatic loss of arterioles. Thus, we have identified 2 important new mechanisms by which low thyroid function may lead to heart failure.

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Authors
Tang, Y.-D., Kuzman, J. A., Said, S., Anderson, B. E., Wang, X., & Gerdes, A. M.
Affiliations
University of South Dakota (US)
ORCID
Venue
Circulation
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2005-11-15
Volume
112
Issue
20
Pages
3122-3130
ISSN
  • 0009-7322 (ISSN-L)
  • 1524-4539
DOI
10.1161/circulationaha.105.572883
OpenAlex
W2150746400
Cited by
179
References
51
Citations by year
2026: 2 · 2025: 8 · 2024: 3 · 2023: 5 · 2022: 7 · 2021: 10 · 2020: 16 · 2019: 7 · 2018: 5 · 2017: 9 · 2016: 11 · 2015: 11 · 2014: 7 · 2013: 12 · 2012: 8
FWCI
4.58
Type
journal article
Language
en
Open access
closed
Locations
  • Circulation (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • University of South Dakota
  • National Institute for Health and Care Research
  • National Institutes of Health (7p20rr017662-07)
  • National Heart, Lung, and Blood Institute (HL 62459, R01HL072166, R01HL062459)
  • National Center for Research Resources (P20-RR-017662)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
Keywords
hypothyroidism, heart failure, cardiac atrophy, myocardial blood flow, systolic dysfunction, propylthiouracil, SERCA2a, myosin heavy chain, phospholamban, left ventricle
MeSH terms
Animals, Atrophy, Blood Flow Velocity, Blood Pressure, Coronary Circulation, Disease Models, Animal, Echocardiography, Female, Cardiomegaly, Heart Rate, Hypothyroidism, Myocardium, Organ Size, Rats, Sprague-Dawley, Rats

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