A role of rising oxygen tension on smooth muscle cell migration in the rat ductus arteriosus

Objective Intimal cushion formation (ICF) is a characteristic vascular remodeling process in the ductus arteriosus (DA). Progressive smooth muscle cell (SMC) migration results in ICF immediately after birth in rodents. We hypothesized that rising oxygen tension plays a role in SMC migration after birth. Methods and Results 1) Isolated SMCs from rat termed-fetal DA were cultured in a hypoxic condition (1% oxygen; the hypoxic group). To investigate the effect of rising oxygen tension on SMC migration, they were transferred in a normoxic condition (21% oxygen; the normoxic group). Using a modified Boyden chamber method, we found that SMC migration was increased by 2.1-fold in the normoxic group when compared with that in the hypoxic group (p<0.05). 2) Since our previous DNA microarray analysis has identified several gene candidates that respond to changes from fetal to neonatal circulation and play a role in migration and proliferation, we examined the direct effect of oxygen on the expression of these genes. Rising oxygen tension from 1% to 21% significantly up-regulated the expression of early growth response gene-1 (3.0-fold), endothelin-1 (2.7-fold), cyclooxygenase-2 (1.9-fold), and fibronectin (1.9-fold) mRNAs in cultured rat DA SMCs. Conclusion Rising oxygen tension promotes migration and regulates gene transcription in rat DA SMCs. These findings may contribute to profound ICF after birth. [J Physiol Sci. 2008;58 Suppl:S189]