Is the vascular system a main target for thyroid hormones? From molecular and biochemical findings to clinical perspectives.
The cardiovascular system is an important target for thyroid hormones (THs). Until recently, our understanding of the biological role of THs has been largely based on a catalog of effects observed in excess or deficiency of THs. In the last decades, however, some important progress has been done in defining the molecular and biochemical basis of thyroid hormone action at the cellular and nuclear level. Most of the molecular and cellular mechanisms responsible for the effects of THs on the heart have been clarified, whereas few data are available about the mechanisms of action of THs on the vasculature. Data reported so far describe the thyroid hormone effects on the vascular system as indirect consequences of thermogenic or hemodynamic derangements. The aim of this review is to focus on the direct role of THs in the vascular system, to analyze the main factors involved in this regulatory process, to evaluate the causes of imbalance, their relationships to some pathophysiological conditions, and, finally, to hypothesize effective therapeutic approaches. Our review considers data on the molecular and biochemical properties of iodothyronine deiodinases, with particular attention to D2, the enzyme for the local conversion of the precursor thyroxine (T4) into the biologically active triiodothyronine (T3). We summarize data on the deiodinase tissue distribution, subcellular localization, topology and structure-activity relationships. We also discuss the physiological role of deiodinases and their involvement in the TH-mediated regulation of vascular function.
Sabatino
Laura
L
Institute of Clinical Physiology, National Council of Research, Pisa, Italy.
Colantuoni
Antonio
A
Iervasi
Giorgio
G
D000595:Amino Acid Sequence; D000818:Animals; D001711:Biotransformation / Q000502:physiology; D006801:Humans; D008969:Molecular Sequence Data; D011988:Receptors, Thyroid Hormone / Q000187:drug effects / Q000235:genetics; D013959:Thyroid Diseases / Q000188:drug therapy / Q000503:physiopathology; D013961:Thyroid Gland / Q000502:physiology / Q000503:physiopathology; D013963:Thyroid Hormones / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use
D011988:Receptors, Thyroid Hormone; D013963:Thyroid Hormones