title: Thyroid hormone is highly permissive in angioproliferative pulmonary hypertension in rats.
abstract: 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 α(v)β(3) 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.
authors: Pulmonary and Critical Care Medicine Division, and Victoria Johnson Center for Pulmonary Ocbstructive Research, Virginia Commonwealth University, Richmond, VA, USA.
authors: Aysar
authors: A
authors: Al Husseini
authors: Gianluca
authors: G
authors: Bagnato
authors: Laszlo
authors: L
authors: Farkas
authors: Jose
authors: J
authors: Gomez-Arroyo
authors: Daniela
authors: D
authors: Farkas
authors: Shiro
authors: S
authors: Mizuno
authors: Donatas
authors: D
authors: Kraskauskas
authors: Antonio
authors: A
authors: Abbate
authors: Benjamin
authors: B
authors: Van Tassel
authors: Norbert F
authors: NF
authors: Voelkel
authors: Harm Jan
authors: HJ
authors: Bogaard
mesh_terms: D000818:Animals; D065627:Familial Primary Pulmonary Hypertension; D006976:Hypertension, Pulmonary / Q000150:complications / Q000209:etiology / Q000473:pathology*; D008297:Male; D009389:Neovascularization, Pathologic / Q000209:etiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013963:Thyroid Hormones / Q000502:physiology*
chemical_list: D013963:Thyroid Hormones