Thyroid Hormone Promotes Remodeling of Coronary Resistance Vessels

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)

Induction of muscularization of small arterioles by T3 treatment of TX rats.

<p>A. Confocal stack projection images of representative arteriolar branch point in thick (30 µm) cryosections; B. Modified morphometric protocol increases the sensitivity of measurement of small arterioles with incomplete VSMC coverage; examples of smaller (top panels) and larger vessels (bottom panels); C. Changes of arteriolar size distribution 72 h after initiation of T3 treatment as compared to arteriolar size distribution in TX rats; α-SMA – alpha smooth muscle actin, IB4 – isolectin B4, SM-MHC – smooth muscle myosin heavy chain. Values are means ± SEM.</p

T3 induces proliferation of microvascular cells in the left ventricle.

<p>A–C. Quantitation of Ki67-positive EC (A), pericytes (B), and VSMC (C); D. Representative images of Ki67-positive nuclei of EC (a–d; IB4⁺), pericytes (e–h; PDGFR-β⁺) and VSMC (i–l; α-SMA⁺) in the left ventricle (100×). Values are means ± SEM; * p<0.05 vs. control, # p<0.05 vs. TX.</p

Thyroid hormone-dependent cardiac mRNA transcripts.

<p>Thyroid hormone-dependent cardiac mRNA transcripts.</p

Arteriolar length density in adult myocardium.

<p>Values are means ± SD. * P<0.05 vs. control; # P<0.05 vs. TX.</p