Thyroid hormone analogue 3,5‐diiodothyropropionic acid (DITPA) promotes healthy vasculature in the adult myocardium independent of thyroid metabolic effects

Abstract

Patients with hypothyroidism are at 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 healthy vasculature, potential undesirable side effects hinder their use in the treatment of vascular disorders. TH analogs such as DITPA may provide a safer treatment option. We hypothesized that the vascular growth promoting effects of DITPA can be obtained with little or no effect on cardiac function and metabolism. Thyroidectomized Sprague Dawley rats were given slow‐release pellets with either thyroxine (T4, 2.7‐mg or 5.2‐mg) or DITPA (80‐mg) for 6 weeks and compared to placebo. Hypothyroidism led to reductions in cardiac function, heart mass, body temperature, and myocardial arterioles. High dose T4 prevented arteriolar loss and 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 progression of hypothyroid‐induced changes in cardiac function and metabolism. Results suggested that DITPA can promote healthy vasculature independently from its thyroid related metabolic effects. Drugs in this class may provide new therapeutic options for patients with vascular disease.Grant Funding SourceP20RR017662 from the National Center for Research Resources