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(Circulation Research. 2001;88:260.)
© 2001 American Heart Association, Inc.

Editorial

Thyroid Hormone

Targeting the Vascular Smooth Muscle Cell

Irwin Klein, Kaie Ojamaa

From the Department of Medicine, Division of Endocrinology, North Shore University Hospital, Manhasset, NY, and Department of Cell Biology, New York University School of Medicine, New York, NY.

Correspondence to Irwin Klein, MD, Chief, Division of Endocrinology, North Shore University Hospital, 300 Community Dr, Manhasset, NY 11030. E-mail iklein@nshs.edu

Key Words: thyroid hormone • vascular resistance • cardiovascular hemodynamics

	Introduction

 
Thyroid hormones (THs) exert marked effects on cardiac function that result from direct effects of the hormones on the cardiac myocyte as well as effects on the peripheral vasculature.¹ The latter effect is best demonstrated by the characteristically high systemic vascular resistance (SVR) observed in patients (and experimental animals) with hypothyroidism, which is rapidly reversed with TH treatment.² Hyperthyroidism produces a marked decrease in SVR, which in turn facilitates an increase in cardiac output and augments peripheral blood flow characteristic of this disease state.^{1 3}

Over 85% of the TH synthesized and released from the thyroid gland is in the form of tetraiodothyronine (thyroxine, T₄). Conversion of T₄ to the biologically active form of the hormone, triiodothyronine (T₃), occurs by 5' monodeiodination (type I 5' deiodinase) primarily in the liver and kidney and, to a smaller extent, by type II 5' deiodinase activity in the pituitary and brain.⁴ In most tissues, the mechanism of TH biological action occurs by the entry of T₃ into the cell by facilitated transport and the binding of T₃ to specific nuclear T₃ receptors (TRs), which regulate transcription of target genes.⁵ In the heart, these genes include contractile proteins (myosin heavy chains) as well as calcium transport/regulatory proteins (sarcoplasmic reticulum calcium–activated ATPase and phospholamban).^{1 6} Nuclear TRs, which belong to the steroid superfamily of transcription factors, bind T₃ with much greater affinity than T₄ and can either positively or negatively regulate transcriptional activity, depending on the presence or absence of T₃ and a T₃-responsive . . . [Full Text of this Article]

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