Abstract
Various animal models have been created for elucidating the pathophysiological mechanisms of pulmonary hypertension (PH) and developing new therapeutics. Each model has its unique characteristics. Comparative transcriptome analysis of two models, in which a phenotype of interest is observed in one but not the other model, can be used to get clues related to the phenotype. In this study, we first compared the transcriptome of lung tissues from two different rat PH models. One model used Su5416, an agonist for aryl hydrocarbon receptor (AhR) and hypoxia to induce PH with the development of neointimal hyperplasia and plexiform layer. Both neointimal hyperplasia and plexiform layer are characteristics in PH patients. The other model used hypoxia only to induce PH in which neointimal hyperplasia and plexiform layer seldom occur. The comparison revealed a cluster of genes with increased expression only in Su5416/hypoxia model. We then compared the transcriptome of lung tissues from Su5416/hypoxia model with and without the treatment of an antagonist for AhR. Integration of these analyses identified several genes that were increased in the Su5416/hypoxia model and regulated by AhR signaling. These genes may be involved in the mechanisms underlying the formation of neointimal hyperplasia and plexiform layer in PH. In this symposium, we would like to demonstrate our study with the validation of these genes using PH model rats and discuss the possibility of these genes as novel therapeutic targets.
