フィンゴリモドはモノクロタリン誘発性肺高血圧症ラットの病態を改善する

抄録

Pulmonary arterial hypertension (PAH) is mainly caused by vasoconstriction and vascular remodeling of the pulmonary artery. This pathogeneses causes sustained elevations in pulmonary arterial pressure and finally leads to right heart failure. Several specific drugs have been recently developed for the treatment of PAH, but are ineffective for some patients. Therefore, additional drugs with different action mechanisms from currently approved drugs are need for the treatment of PAH. We previously found that fingolimod inhibited the excessive proliferation of pulmonary arterial smooth muscle cells (PASMCs) from idiopathic PAH patients and improved the survival rate of monocrotaline-induced pulmonary hypertensive (MCT-PH) rats. In the present study, we examined whether fingolimod blocked pulmonary vascular remodeling. The medial hypertrophy in small pulmonary arteries was more marked in MCT-PH rats than sham rats. Intraperitoneal administration of fingolimod blocked the development of pulmonary vascular remodeling. In addition, an increase in right ventricular systolic pressure in MCT-PH rats was also reduced by fingolimod. Our results strongly suggest that fingolimod ameliorates pulmonary vascular remodeling by inhibiting the proliferation of PASMCs. Fingolimod may be a novel drug for the treatment of PAH.