Thyroid hormone analog 3,5-diiodothyropropionic acid promotes healthy vasculature in the adult myocardium independent of thyroid effects on cardiac function

Abstract

Liu Y, Wang D, Redetzke RA, Sherer BA, Gerdes AM. Thyroid hormone analog 3,5-diiodothyropropionic acid promotes healthy vasculature in the adult myocardium independent of thyroid effects on cardiac function. Am J Physiol Heart Circ Physiol 296: H1551-H1557, 2009. First published March 13, 2009; doi:10.1152/ajpheart.01293.2008Patients with hypothyroidism are at a higher risk for coronary vascular disease. Patients with diabetes and related vascular complications also have an increased incidence of low thyroid function. While thyroid hormones (THs) may be key regulators of a healthy vasculature, potential undesirable side effects hinder their use in the treatment of vascular disorders. TH analogs such as 3,5-diiodothyropropionic acid (DITPA) may provide a safer treatment option. However, the relative potency of DITPA on vascular growth, cardiac function, and metabolism is poorly understood. We hypothesized that the vascular growth-promoting effects of DITPA can be obtained with a minimum effect on cardiac function. Thyroidectomized Sprague-Dawley rats were given slow-release pellets with either thyroxine (T4, 2.7 or 5.2 mg) or DITPA (80 mg) for 6 wk and were compared with placebo. Heart mass, body mass, body temperature, serum THs, cardiac function (echocardiograms and hemodynamics), and myocardial arteriolar density were determined. Hypothyroidism led to reductions in cardiac function, heart mass, body temperature, and myocardial arterioles. High-dose T4 prevented arteriolar loss and the development of hypothyroidism. Low-dose T4 partially prevented the reduction in cardiac function but had minimal effects on arteriolar loss. In contrast, DITPA treatment prevented myocardial arteriolar loss but not the progression of hypothyroid-induced changes in cardiac function. The results suggested that DITPA can promote a healthy vasculature independently from its thyroid-related metabolic effects. Drugs in this class may provide new therapeutic options for patients with vascular disease.hypothyroidism; myocardial arterioles; vascular disease HYPOTHYROIDISM HAS BEEN LINKED to a variety of cardiovascular diseases, such as myocardial infarction (9), coronary atherosclerosis (5), and congestive heart failure (2). Thyroid hormone (TH) supplementation can increase cardiac contractility (16), promote cardiac hypertrophy (7), and induce vasodilatation (22). Tomanek et al. (29) have shown that THs are proangiogenic and can stimulate angiogenesis and arteriolar growth in normal hearts. We have shown that TH treatment of rats during an induction of hypothyroidism prevents the associated loss of arterioles (15). These beneficial effects of THs make them potentially attractive for the use of treating various cardiovascular diseases. However, concerns have been raised about the potential undesirable adverse effects such as increased heart rate and metabolism.It has been shown that the TH analog 3,5-diiodothyropropionic acid (DITPA) has inotropic selectivity (23) due partly to the enhanced release of sarcoplasmic reticulum calcium (11) ...

Low-Dose T3 Replacement Restores Depressed Cardiac T3 Levels, Preserves Coronary Microvasculature and Attenuates Cardiac Dysfunction in Experimental Diabetes Mellitus

“…Our findings are consistent with reports noting that reversing cardiac hypothyroidism by THs or their analogues can preserve the small arteriole resistance vessel network (14,34,42,56,57). Moreover, we have previously shown that the TH analogue DITPA (3,5-diiodothyropropionic acid) can prevent arteriolar loss in hypothyroid rodents independent of cardiac function (61). The above findings suggest that the combined influence of THs on arteriolar vascular tone and density and the preserved gene expression of vascular regulators are likely to reverse the increased coronary vascular resistance and to improve blood flow in diabetic hearts.…”

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Influence of thyroid state on cardiac and renal capillary density and glomerular morphology in rats

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