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 THmediated regulation of vascular function.
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 THmediated regulation of vascular function.
Keywords: angiogenesis; catecholamines; endothelial dysfunction; iodothyronine monodeiodinases; thyroid hormone analogs; thyroid hormone receptors; thyroid hormones; vascular tone
Document Type: Review Article
Affiliations: Institute of Clinical Physiology, CNR Via Moruzzi 1, San Cataldo, 56124 Pisa, Italy.
Publication date: 01 April 2005
- Vascular disease is the commonest cause of death in Westernized countries and its incidence is on the increase in developing countries. It follows that considerable research is directed at establishing effective treatment for acute vascular events. Long-term treatment has also received considerable attention (e.g. for symptomatic relief). Furthermore, effective prevention, whether primary or secondary, is backed by the findings of several landmark trials.
Vascular disease is a complex field with primary care physicians and nurse practitioners as well as several specialties involved. The latter include cardiology, vascular and cardio thoracic surgery, general medicine, radiology, clinical pharmacology and neurology (stroke units). Current Vascular Pharmacology will publish reviews to update all those concerned with the treatment of vascular disease. For example, reviews commenting on recently published trials or new drugs will be included. In addition to clinically relevant topics we will consider 'research-based' reviews dealing with future developments and potential drug targets. Therefore, another function of Current Vascular Pharmacology is to bridge the gap between clinical practice and ongoing research.
Debates will also be encouraged in the correspondence section of this journal. - Editorial Board
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