Potential therapeutic target for pulmonary arterial hypertension--osteopontin

Microarray analysis demonstrated lung gene encoding osteopontin (OPN), a soluble secreted phosphoprotein, was significantly elevated in rats with hypoxic pulmonary arterial hypertension (PAH). Since OPN enhances vascular smooth muscle cell proliferation, we hypothesized that OPN played a role in the pathogenesis of PAH. Some patients with idiopathic PAH showed increased expression of plasma OPN and lung OPN gene. OPN overexpression in mice caused pronounced pulmonary hypertension and vascular remodeling under hypoxic conditions. A PPARgamma ligand, pioglitazone, which was reported to inhibit OPN gene expression in vitro, attenuated hypoxia-induced increase in lung OPN gene and pulmonary vascular remodeling in rats. These findings indicate that OPN may be responsible for pulmonary vascular remodeling and could be a therapeutic target for PAH.