Resumen:
Hypothyroidism is an independent risk factor for cardiovascular disease and, if chronically sustained, leads to myocardial contractile dysfunction resulting in heart failure. However, the subcellular mechanisms underlying contractile dysfunction are not completely understood. It has been suggested that abnormal gene expression in the myocardium triggered by decreased thyroid hormone plasma levels reduces the expression of sarco-/endoplasmic reticulum calcium ion (Ca2+) adenosine triphosphatase (SERCA), resulting in slower sarcoplasmic reticulum (SR) Ca2+ uptake, a decrease in SR Ca2+ content and reduced SR Ca2+ release that mediates contractile dysfunction [1]. However, in addition to the decrease in thyroid hormones, hypothyroidism is characterised by increased thyrotropin (TSH) levels. Interestingly, subclinical hypothyroidism, which is defined by increased TSH with normal T3 and T4 levels, is also associated with altered contractile dysfunction [2], suggesting that TSH could contribute to reduced contractility observed in hypothyroidism. However, whether and how TSH impacts adult cardiac myocyte contractile function has never been addressed. This study aims to investigate whether TSH affects Ca2+ dynamics, Ca2+ handling protein expression, and contractile function in adult rat cardiac myocytes and in human-induced pluripotent stem cell-derived cardiac myocytes.
