TY - JOUR T1 - Thyroid hormone is highly permissive in angioproliferative pulmonary hypertension in rats JF - European Respiratory Journal JO - Eur Respir J SP - 104 LP - 114 DO - 10.1183/09031936.00196511 VL - 41 IS - 1 AU - Aysar Al Husseini AU - Gianluca Bagnato AU - Laszlo Farkas AU - Jose Gomez-Arroyo AU - Daniela Farkas AU - Shiro Mizuno AU - Donatas Kraskauskas AU - Antonio Abbate AU - Benjamin Van Tassel AU - Norbert F. Voelkel AU - Harm Jan Bogaard Y1 - 2013/01/01 UR - http://erj.ersjournals.com/content/41/1/104.abstract N2 - Epidemiological evidence links pulmonary arterial hypertension (PAH) with thyroid disease, but a mechanistic explanation for this association is lacking. Because a central hallmark of vascular remodelling in pulmonary hypertension is lumen obliteration by endothelial cell growth and because thyroid hormones are known to be angiogenic, we hypothesised that thyroid hormones play a role in the control of endothelial cell proliferation in experimental PAH in rats. Hypothyroidism was induced by subtotal thyroidectomy and treatment with propylthiouracil (PTU) in rats with experimental PAH after combined exposure to vascular endothelial growth factor receptor inhibition and hypoxia (the Sugen-chronic hypoxia (SuHx) model). Subtotal thyroidectomy prevented and PTU treatment reversed the development of severe experimental PAH. Thyroxin repletion restored the PAH phenotype in thyroidectomised SuHx rats. The prevention of PAH by thyroidectomy was associated with a reduced rate of cell turnover, reduced extracellular signal-regulated protein kinases 1 and 2 phosphorylation, and reduced expression of αvβ3 integrin, fibroblast growth factor (FGF)-2 and FGF receptor. Thyroidectomy mitigated hypoxia-induced pulmonary hypertension, but this effect was not associated with a decreased pulmonary vascular resistance. These data suggest that thyroid hormone permits endothelial cell proliferation in PAH. A causal link between thyroid diseases and the onset or progression of vascular remodelling in PAH patients remains to be determined. ER -