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.

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

“…Although TH and analogues are pro-angiogenic in various models, as reported earlier, their effects at the microvascular level remain controversial, with reports of unchanged (Wachtlova et al 1985, Breisch et al 1989, Heron & Rakusan 1994 or even reduced (Gerdes et al 1979, Weiss & Grover 1987, Tomanek et al 1995, Anjos-Ramos et al 2006 cardiac capillary density in hyperthyroid rats. Cardiac capillary density was found to be increased in hypothyroid rats (Heron & Rakusan 1994) and rabbits (Tomanek et al 1993).…”

Possible Relation of Hemin-Induced HO-1 Expression to the Upregulation of VEGF and BDNF mRNA Levels in Rat C6 Glioma Cells

“…Total RNA (3 μg) was incubated at 48°C for 45 min in 25 μl of the first strand buffer (75 mM KCl, 3 mM MgCl 2 , and 50 mM Tris-HCl, pH 8.3) containing 500 μM deoxyribonucleotide triphosphates, 400 μM dithiothreitol, 5% dimethylsulfoxide, 25 pmol of the primers using 100 U of M-MLV reverse transcriptase and 2.5 U of recombinant Taq DNA polymerase. Basically, according to the PCR conditions reported previously (Anjos-Ramos et al 2006;Bova et al 1998;Marton et al 2000), the first strand cDNA was successively amplified by subjecting the reaction mixture to 35 cycles of DNA polymerase chain reaction with each cycle including the steps of denaturation at 95°C for 1 min, primer annealing at 60°C (HO-1), 70°C (VEGF), and 56°C (BDNF) for 1 min, primer extension at 72°C for 1 min, and a final extension step at 72°C for 7 min. The PCR products were separated on a 1.8% agarose gel, and the signal intensities of the bands were then determined by computerized densitometric analysis using the Scion Image for Windows 4.02 software.…”

MECHANISMS IN ENDOCRINOLOGY: Heart failure and thyroid dysfunction

“…Integrin a v b3 contains a cell surface receptor site for thyroid hormone that is linked to activation of mitogen-activated protein kinase and induction of angiogenesis (30). Vascular endothelial growth factor and fibroblast growth factor are implicated in thyroid hormone-induced angiogenesis (31). TRb is required for angiogenesis during cardiac development (32).…”