Tissue thyroid hormones and thyronamines.
It has been known for a long time that changes in cardiac function are a major component of the clinical presentation of thyroid disease. Increased heart rate and hyperdynamic circulation are hallmarks of hyperthyroidism, while bradycardia and decreased contractility characterize hypothyroidism. Recent findings have provided novel insights in the physiology and pathophysiology of heart regulation by thyroid hormones. In this review, we summarize the present knowledge on thyroxine (T4) transport and metabolism and on the biochemical pathways leading to genomic and non-genomic effects produced by 3,5,3'-triiodothyronine (T3) and by its active metabolites, particularly 3,5-diiodothyronine (T2) and 3-iodothyronamine (T1AM). On this basis, specific issues of special interest for cardiology are discussed, namely (1) relevance of the regulation of proteins involved in the control of calcium homeostasis and in pacemaker cell activity, due to non-genomic as well as to classical genomic effects; (2) stimulation of fatty acid oxidation by T2 and T1AM, the latter also causing a negative inotropic and chronotropic action at micromolar concentrations; (3) induction of D3 deiodinase in heart failure, potentially causing selective cardiac hypothyroidism, whose clinical implications are still controversial; and (4) cardioprotective effect of T1AM, possibly occurring at physiological concentrations, and relevance of T3 and of thyroid hormone receptor α1 in post-infarction repair.
Scuola Superiore Sant'Anna, Pisa, Italy.
Alice
A
Accorroni
Scuola Superiore Sant'Anna, Pisa, Italy.
Federica
F
Saponaro
Laboratory of Biochemistry, Department of Pathology, University of Pisa, via Roma 55, 56126, Pisa, Italy. riccardo.zucchi@med.unipi.it.
Riccardo
R
Zucchi
D000818:Animals; D004195:Disease Models, Animal; D006321:Heart / Q000503:physiopathology*; D006333:Heart Failure / Q000209:etiology / Q000503:physiopathology; D006801:Humans; D006980:Hyperthyroidism / Q000150:complications*; D007037:Hypothyroidism / Q000150:complications*; D050356:Lipid Metabolism; D051379:Mice; D051381:Rats; D013963:Thyroid Hormones / Q000235:genetics / Q000502:physiology*
D013963:Thyroid Hormones
3,5-Diiodothyronine; 3-Iodothyronamine; Heart failure; Ischemia; Thyroid hormone