Thyroid dysfunction is common in individuals with diabetes mellitus (DM) and may contribute to the associated cardiac dysfunction. However, little is known about the extent and pathophysiological consequences of low thyroid conditions on the heart in DM. DM was induced in adult female SD rats by injection of nicotinamide (N; 200 mg/kg) followed by streptozotocin (STZ; 65 mg/kg). One month after STZ/N, rats were randomized to the following groups (N=10/group): STZ/N or STZ/N + 0.03 μg/ml T3; Age-matched vehicle treated rats served as non-diabetic controls (C). After 2 months T3 treatment (3 months post DM induction), LV function was assessed by echocardiography and LV pressure measurements. Despite normal serum thyroid hormone (TH) levels, STZ/N treatment resulted in reductions in myocardial tissue content of THs (T3 & T4: 39% & 17% reduction vs. C, respectively). Tissue hypothyroidism in the DM hearts was associated with increased D3 deiodinase (which converts THs to inactive metabolites) and TH transporter expression, re-expression of the fetal gene phenotype, reduced arteriolar resistance vessel density, and diminished cardiac function. Low-dose T3 replacement largely restored cardiac tissue TH levels (T3 & T4: 43% & 10% increase vs. STZ/N, respectively), improved cardiac function, reversed fetal gene expression, and preserved the arteriolar resistance vessel network without causing overt symptoms of hyperthyroidism. We conclude that cardiac dysfunction in chronic DM may be associated with tissue hypothyroidism despite normal serum TH levels. Low-dose T3 replacement appears to be a safe and effective adjunct therapy to attenuate and/or reverse cardiac remodeling and dysfunction induced by experimental DM.
|Autori interni:||ZUCCHI, RICCARDO|
|Autori:||Weltman NY; Ojamaa K; Schlenker EH; Chen YF; Zucchi R; Saba A; Colligiani D; Rajagopalan V; Pol CJ; Gerdes AM.|
|Titolo:||Low-dose T3 replacement restores depressed cardiac T3 levels, preserves coronary microvasculature, and attenuates cardiac dysfunction in experimental diabetes mellitus.|
|Anno del prodotto:||2014|
|Digital Object Identifier (DOI):||10.2119/molmed.2013.00040|
|Appare nelle tipologie:||1.1 Articolo in rivista|