Thyroid Hormone Promotes Remodeling of Coronary Resistance Vessels

Abstract

Low thyroid hormone (TH) function has been linked to impaired coronary blood flow, reduced density of small arterioles, and heart failure. Nonetheless, little is known about the mechanisms by which THs regulate coronary microvascular remodeling. The current study examined the initial cellular events associated with coronary remodeling induced by triiodothyronine (T3) in hypothyroid rats. Rats with established hypothyroidism, eight weeks after surgical thyroidectomy (TX), were treated with T3 for 36 or 72 hours. The early effects of T3 treatment on coronary microvasculature were examined morphometrically. Gene expression changes in the heart were assessed by quantitative PCR Array. Hypothyroidism resulted in arteriolar atrophy in the left ventricle. T3 treatment rapidly induced small arteriolar muscularization and, within 72 hours, restored arteriolar density to control levels. Total length of the capillary network was not affected by TX or T3 treatment. T3 treatment resulted in the coordinate regulation of Angiopoietin 1 and 2 expression. The response of Angiopoietins was consistent with vessel enlargement. In addition to the well known effects of THs on vasoreactivity, these results suggest that THs may affect function of small resistance arteries by phenotypic remodeling of vascular smooth muscle cells (VSMC).

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

“…These haemodynamic and metabolic factors prevent the increase in HIF-1a and hence the triggering of an angiogenic response mediated by VEGF, bFGF or angiogenin. The greater cardiac capillary density in the hypothyroid group is in agreement with previous findings in rats (Heron & Rakusan 1994, Savinova et al 2011) and rabbits (Tomanek et al 1993). The cardiac capillary response to hypothyroidism is thought to be similar to that of bradycardially paced hearts, in which capillary densities are increased (Tomanek et al 1993.…”

“…The reduction in myocyte diameter may be responsible for this increase, given that the hypothyroidism-induced myocardial atrophy would bring capillaries closer together, thereby increasing the number of capillaries per square millimetre of tissue. Savinova et al (2011) reported an increased capillary density in the cardiac ventricle of thyroidectomised (TX) female rats that correlated with LV weight when controls and TX rats were pooled in a common regression line. However, TX rats showed a reduction of around 28% in LV weight/body weight ratio and an increase of around 66% in myocardial capillary density.…”

MECHANISMS IN ENDOCRINOLOGY: Heart failure and thyroid dysfunction

“…TRb is required for angiogenesis during cardiac development (32). Thyroid hormones are powerful regulators of vessel overgrowth in the hypothyroid state; they promote coronary arteriolar and capillary growth (33).…”

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

“…FITCIsolectin-B4 (IB4; Vector, Burlingame, CA, USA) and Cy3-α-smooth muscle actin (α-SMA; Sigma-Aldrich) were used in combination to label endothelial cells and vascular smooth muscle cells respectively. Arteriolar numeric density (ND), arteriolar length density (LD), capillary ND density, and total capillary length were quantified using previously described methods (34,35).…”