Thyroid hormone disorder and the heart: The role of cardiolipin in calcium handling

Exp Physiol. 2023 Mar;108(3):412-419. doi: 10.1113/EP090817. Epub 2023 Jan 18.

Abstract

New findings: What is the central question of this study? Do alterations in thyroid status affect haemodynamic parameters and echocardiographic measurements in the rat postnatal heart, and calcium handling, contractility, relaxation and cardiolipin content in isolated rat cardiomyocytes? What is the main finding and its importance? An imbalance in phospholipids of the mitochondrial membrane such as cardiolipin is related to defects in mitochondrial function. T3 -dependent cardiolipin signals contribute to the maintenance of mitochondrial homeostasis and involve Ca2+ handling, this pathway being more important in hypothyroidism.

Abstract: The objective of this study was to evaluate whether alterations in thyroid status affect (1) haemodynamic parameters and echocardiographic measurements in the rat postnatal heart, and (2) calcium handling, contractility, relaxation and cardiolipin content in isolated rat cardiomyocytes. Sprague-Dawley rats aged 2 months treated with T3 (hyperthyroid, 20 μg/100 g body weight) or 0.02% methimazole (hypothyroid, w/v) for 28 days. Heart function was evaluated by echocardiography. Measurements of mean arterial pressure (MAP), heart rate, Ca2+ transients, cardiomyocyte shortening, number of spontaneous contractions per minute and cardiolipin (CL) content were performed. Thyroid disorders were associated with changes in pacemaker activity without modifications of MAP. Thyroid disorder induced changes in left ventricular diameter which were correlated with modifications of cardiac contractility (altered cell shortening and sarcoplasmic reticulum Ca2+ content). Endocrine disorders altered cardiomyocyte relaxation (reduction in the time to 50% re-lengthening and the time to 50% Ca2+ decay). Thyroid disorder increased the number of spontaneous contractions per minute (an index of pro-arrhythmogenic behaviour). CL content was increased only in hypothyroid rats. Changes in CL content, CL composition and CL-protein interaction in mitochondria from hypothyroid animals are responsible for alterations of contractile and relaxation cardiac function. This mechanism may be not be involved in T3 -treated rats. Maintenance of euthyroidism is of crucial importance to preserve cardiac performance. An imbalance in relation to phospholipids of the mitochondrial membrane such as CL is related to defects in mitochondrial function. T3 -dependent CL signals contribute to the maintenance of mitochondrial homeostasis and involve Ca2+ handling, this pathway being more important in hypothyroidism.

Keywords: calcium; cardiolipin; heart; thyroid hormone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / metabolism
  • Cardiolipins* / metabolism
  • Hypothyroidism*
  • Myocardial Contraction
  • Myocytes, Cardiac / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Sarcoplasmic Reticulum / metabolism
  • Thyroid Hormones / metabolism

Substances

  • Cardiolipins
  • Calcium
  • Thyroid Hormones