シンポジウム10（I-S10）
小児の肺動脈性肺高血圧へのアプローチ：最近のエビデンス

[I-S10-04] 肺動脈性肺高血圧への早期治療の分子基盤：閉塞性肺血管病変を伴う動物モデルの網羅的遺伝子解析

^○大槻 祥一郎¹, 三谷 義英¹, 篠原 務⁴, 澤田 博文², 淀谷 典子¹, 加藤 太一⁵, 大橋 啓之¹, 張 尓泉², 新保 秀人³, 丸山 一男², 平山 雅浩¹ (1.三重大学 小児科 麻酔科, 2.三重大学 麻酔科, 3.三重大学 心臓血管外科, 4.名古屋市立大学 小児科, 5.名古屋大学 小児科)

(Background) We previously reported that immature smooth muscle cells and macrophages contribute to the development of occlusive pulmonary vascular disease (PVD) in the Sugen/hypoxia-treated (SH) rats, and that macitentan partially reversed PVD in such models in the early treatment (3-5 weeks) but not in the late treatment (5-8 weeks). However, the molecular basis of the treatment is speculative. We therefore tested the hypothesis that differentially expressed genes, the related cellular processes, and transcriptional regulators are associated with the effects of the compound in PAH. (Methods) Lists of differentially expressed genes were analyzed to predict related cell process and the transcriptional regulators, by using lung samples from controls and macitentan or vehicle-treated SH rats in the early or late treatment period. (Results) 427 and 460 genes were differentially regulated in SH rats in the early and late treatment periods, respectively, in which 102 and 78 genes were regulated by macitentan, respectively. Genes especially related to inflammatory processes and cell differentiation were differentially expressed in PAH and regulated by macitentan treatment in SH rats in the early treatment. As for PAH-related genes, some inflammatory genes which was upregulated in PAH and reversed by macitentan in the early treatment was distinct from those in the late treatment; some inflammatory genes which was upregulated by PAH and negatively regulated by macitentan in the early treatment became unresponsive to the treatment in the late period. (Conclusions) These bioinformatics analysis may confer a molecular basis of the early treatment and resistance to treatment in this disorder.