2003 Fiscal Year Final Research Report Summary
Role of anti-BMP receptor antibodies in the development of pulmonary hypertension
| Project/Area Number |
14570542
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | Chiba University |
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Principal Investigator |
KURASAWA Kazuhiro Chiba University, Graduate School of Medicine, Lecturer, 大学院・医学研究院, 講師 (30282479)
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| Co-Investigator(Kenkyū-buntansha) |
IWAMOTO Itsuo Chiba University, Graduate School of Medicine, Associate Professor, 大学院・医学研究院, 助教授 (10111436)
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| Project Period (FY) |
2002 – 2003
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| Keywords | Pulmonary Hypertension / Collagen-Vascular disease / BMP (bone morphogenetic protein) / BMP receptor / Autoantibodies / Pulmonary Artery Smooth Muscle Cells |
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| Research Abstract |
Pulmonary hypertension (PH)is a critical complication of collagen vascular diseases (CVD). The etiological mechanisms of PH in CVD are largely unknown. Recent studies have shown that familial PH is caused by mutations of bone morphogenetic protein receptor type II (BMPR-II), which block inhibitory effect of bone morphogenetic protein (BMP) on proliferation of pulmonary artery smooth muscle cells (PASm). We, therefore, hypothesized that PH is caused by autoantibodies against BMPR-II which block BMP signaling and induce abnormal proliferation of smooth muscle cells. The aim of this study is to verify this hypothesis. To detect auto-antibodies against BMPR-II, we performed flowcytometry analysis using BMPR-II transfectants that expressed BMPR-II on their surface as antigen. This analysis showed that 5 out of 14 (35%) CVD patients with PH are positive for anti-BMPR-II antibodies, whereas none of those without PH or wealthy subjects were positive for the antibodies. Furthermore, anti-BMPR-II antibodies was detected in a PH patient before the onset of PH. In addition, titer of the antibodies were changed related pulmonary artery pressure in patients treated with immuno-suppressive therapy. We examined whether serum of anti-BMPR-II antibodies block. BMP signaling. serum with anti-BMPR-II antibodies blocked BMP inhibitory effects on proliferation of PASm.. These results have shown that there exist anti-BMP receptor antibodies in some cases of PH in CVD and antibodies might be involved in the development of PH by blocking of BMP signals that inhibits proliferation of PASm, and indicate that measuring of anti-BMP receptor antibodies is of valuable for prediction and monitoring of PH.
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