Molecular mechanism of Vasculitis and Pulmonary arterial hypertension via inflammatory cytokines

2016 Fiscal Year Final Research Report

• Project/Area Number: 15K15309
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Cardiovascular medicine
• Research Institution: National Cardiovascular Center Research Institute
• Principal Investigator: Nakaoka Yoshikazu 国立研究開発法人国立循環器病研究センター, 研究所, 部長 (90393214)
• Co-Investigator(Renkei-kenkyūsha): SHIRAI MIKIYASU 国立循環器病研究センター, 研究所, 特任研究員 (70162758) ; HOSEN NAOKI 大阪大学, 大学院医学系研究科, 准教授 (10456923)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Keywords: 炎症 / サイトカイン / 肺動脈性肺高血圧症 / 高安動脈炎 / interleukin-6 / interleukin-21

Outline of Final Research Achievements

We aimed to elucidate the molecular mechanisms of intractable　vascular　diseases　such　as　Takayasu　arteritis　(TAK) or　pulmonary　arterial　hypertension　(PAH) in this study.　We tried to create the animal models of these diseases which mimic the pathologies of these diseases through overexpression of the key inflammatory cytokines in the aortic endothelium or lung epithelium. We hypothesized that inflammatory cytokines including interleukin-6 (IL-6) or IL-21 are important for development of TAK of PAH, and created the mice which harbor the TetO-mIL-6 or TetO-mIL-21 genes in C57BL6 mice for creation of PAH model mice. And, we also created transgenic mice which harbor either BMX-mIL-6 or BMX-mIL-21. Until now, we could not succeed in creating the above transgenic mice which overexpress mIL-6 or mIL-21 either in aortic endothelium or in lung epithelium. We are now adjusting the overexpression condition in the above TG mice.

Free Research Field

循環器内科学、血管病学、炎症性サイトカインの生物学