Our previous work has demonstrated that the cellular phenotype changes of human pulmonary artery smooth muscle cells (PASMCs) play an important role during pulmonary vascular remodelling. However, little is known about the role of PASMCs phenotype modulation in the course of hypoxia-induced migration and its behind molecular mechanisms. In this study, we have shown that cGMP-dependent protein kinase (PKG) I alpha transfection significantly attenuated the hypoxia-induced down-regulation of the expressions of SM-alpha-actin, MHC and calponin. Hypoxia-induced PASMC migration was also suppressed by PKGI alpha. overexpression. Furthermore, this overexpression attenuated ANX A1 upregulation under hypoxic conditions. All those effects were reversed by a PKG inhibitor KT5823. Our data indicate that manipulating upstream entity e.g., PKGIa, may have a potential therapeutic value to prevent hypoxia-associated pulmonary arterial remodeling for pulmonary hypertension development. (C) 2012 Elsevier Inc. All rights reserved.