フィンゴリモドは肺動脈性肺高血圧症における炎症を抑制し、肺血管リモデリングを改善する

抄録

Pulmonary arterial hypertension (PAH) is classified as group 1 of pulmonary hypertension and designated intractable disease. The pathogenesis is mainly caused by vasoconstriction and vascular remodeling of the pulmonary artery. These abnormalities lead to sustained elevations in pulmonary arterial pressure and finally cause right heart failure. Several drugs have been recently developed, but those are mainly pulmonary vasodilators and ineffective for severe PAH. Therefore, novel drugs are awaited as therapeutic strategy of PAH. Previously, we found that the expression of sphingosine-1-phosphate (S1P) receptors was upregulated in PAH patients. Those modulator “fingolimod” blocked vascular remodeling and improved the survival rate of monocrotaline-induced pulmonary hypertensive (MCT-PH) rats. Fingolimod is an immunosuppressant drug that is used to treat multiple sclerosis, therefore, we herein examined whether fingolimod reduced inflammation in PAH. The accumulation of macrophages was detected in remodeled vascular legions of MCT-PH rats, which was reduced by the administration of fingolimod. In addition, fingolimod inhibited the proliferation of macrophages. Our results suggest that fingolimod ameliorates the development of PAH by blocking pulmonary vascular remodeling as a result of the reduction of inflammation.