[P45-04] モノクロタリンと低酸素環境によるラット肺高血圧モデルにおいてCXCR4とMSCマーカーに高発現が観察された
キーワード：Pulmonary arterial hypertension, CXCR4, Mesenchymal stem cells
Background: Pulmonary arterial hypertension (PAH) is characterized by a severe and fatal clinical syndrome. C-X-C chemokine receptor type 4 (CXCR4) is known to play a key role in recruiting mesenchymal stem cells (MSCs) from the bone marrow. CXCR4 inhibitors has been reported not only to inhibit tumor cell migration and proliferation, but also to ameliorate pulmonary arterial muscularization. Purpose: Therefore, we established rat PAH models to investigate involvement of CXCR4 and MSCs in developing PAH. Methods: PAH in rats was induced by 5 weeks of chronic hypoxia and treatment with a single injection of monocrotaline (60 mg/kg). We measured the gene/protein expression levels of CXCR4 and stem cell/MSC markers, and then compared PAH experimental groups with controls. Results: Successful establishment of the PAH models was confirmed by differences between PAH and control groups in right ventricular systolic pressure, Fulton index, and medial wall thickness as well as vascular occlusion score determined by immunohistochemical staining. Reverse Transcription quantitative Polymerase Chain Reaction (RT-qPCR) showed that the expression of CXCR4 SCF, c-Kit, and CD29, was significantly higher in the PAH group, which are known to be expressed in MSCs. Immunohistochemical staining also showed that the expression of CXCR4, c-Kit, and CD90 was significantly higher in the PAH group. Conclusion: These results indicate that CXCR4 and MSCs may be involved in the pathogenesis of PAH. At the same time, stem cells may play an important role in pulmonary vascular remodeling.