cGMP-dependent protein kinase Iα transfection inhibits hypoxia-induced migration, phenotype modulation and annexins A1 expression in human pulmonary artery smooth muscle cells

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) Iα transfection significantly attenuated the hypoxia-induced down-regulation of the expressions of SM-α-actin, MHC and calponin. Hypoxia-induced PASMC migration was also suppressed by PKGIα 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.

► Human PASMCs was used in this study.
► Hypoxia-induced phenotype modulation was suppressed by the transfer of Ad-PKGIα.
► The inhibition of phenotype modulation reversed hypoxia-induced PASMC migration.
► ANX A1 might mediate this inversion effect.
► Phenotype modulation and its molecular mechanism was a key cure target in future.