Thyroid hormone is highly permissive in angioproliferative pulmonary hypertension in rats.
Eur Respir J. 2012 Jul 26;
Authors: Al Husseini A, Bagnato G, Farkas L, Gomez-Arroyo J, Farkas D, Mizuno S, Kraskauskas D, Abbate A, Van Tassel Pharm D B, Voelkel NF, Bogaard HJ
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 hypothesized 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 VEGF-R inhibition and hypoxia (the SuHx model). Subtotal thyroidectomy prevented and PTU treatment reversed the development of severe experimental PAH. T4 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 Erk1/2 phosphorylation, and reduced expression of ?v?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 remodeling in PAH patients remains to be determined.
PMID: 22835607 [PubMed - as supplied by publisher]
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