Early cardiac hypertrophy induced by thyroxine is accompanied by an increase in VEGF-A expression but not by an increase in capillary density

Abstract

Cardiac hypertrophy in response to hyperthyroidism is well known. However, the effects on cardiac microcirculation are still controversial in this model. The present study evaluated the effects of acute administration of two different thyroxine (T4) dose levels on the angiogenic response in the myocardium. Capillary density (CD), the CD to fiber density (FD) ratio (CD/FD), and intercapillary distance (ICD) were assessed, as was ventricle weight (VW) to body weight (BW) ratio (VW/BW). Collagen I and III messenger ribonucleic acid (mRNA) expression and VEGF-A expression were also determined by reverse transcriptase polymerase chain reaction (RT-PCR). Immunohistochemical detection of proliferating cell nuclear antigen (PCNA) expression in endothelial cell nuclei was also carried out. We simulated an acute hyperthyroidism situation in male Wistar rats by daily intraperitoneal injection of T4 (0.025 or 0.1 mg kg(-1) day(-1)) for 7 days. Hemodynamic parameters showed that T4 did not alter systolic blood pressure (SBP) but significantly increased heart rate (HR). Both T4 doses significantly increased VW. Morphologically, the higher T4 dose resulted in a 33% greater myocardial mass, which was not accompanied by alterations in collagen I and III mRNA expression. The CD and CD/FD parameters were significantly lower in the hyperthyroid rats treated with the higher dose than in the control animals, and PCNA-labeling analysis indicated total absence of marked capillary growth. However, although the acute treatment with T4 did not induce any alteration in capillary number and endothelial cell proliferation, the vascular endothelial growth factor (VEGF)-A mRNA and protein expression were significantly increased with the higher T4 dose. These data indicate that the cardiac hypertrophy induced by acute treatment with thyroid hormone precedes the angiogenic process, which probably occurs later.