2005 Fiscal Year Final Research Report Summary
Decoy therapy for monocrotaline-induced pulmonary hypertension and neointimal formation in rats
| Project/Area Number |
16591566
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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 |
Anesthesiology/Resuscitation studies
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| Research Institution | The Jikei University School of Medicine (2005)
Tokyo Women's Medical University (2004) |
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Principal Investigator |
UEZONO Shoichi The Jikei University School of Medicine, Professor, 医学部, 教授 (10291676)
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| Co-Investigator(Kenkyū-buntansha) |
ODA Hideaki Tokyo Women's Medical University, School of Medicine, Professor, 医学部, 教授 (40214142)
KONDO Izumi Tokyo Women's Medical University, School of Medicine, Lecturer, 医学部, 講師 (80170421)
YAMAGATA Katsuyuki Tokyo Women's Medical University, School of Medicine, Research Assistant, 医学部, 助手 (10328461)
KOMORI Makiko Tokyo Women's Medical University, School of Medicine, Research Assistant
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| Project Period (FY) |
2004 – 2005
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| Keywords | Pulmonary hypertension / vascular remodeling / neointima formation / Egr-1 / decoy therapy / NF-kB |
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| Research Abstract |
Background : Hypertensive pulmonary vascular disease is characterized by abnormal proliferation of vascular endothelial and smooth muscle cells, leading to occlusion of pulmonary arterioloes, PH, right ventricular failure and death. Egr-1 is a transcription factor that is rapidly activated after vascular injury and thus might contribute to vascular proliferation and inflammation. Therefore, we hypothesized that Egr-1 might be a therapeutic target for PH. To achieve effective suppression of Egr-1 in vivo, transfection with synthetic double-stranded Egr-1 decoy oligodeonucleotides was utilized in this study.
Results : Successful introduction of Egr-1 decoy into pulmonary vessels was confirmed by using fluorescein isothiocyanate (FITC)-labeled decoy. Transfection of Egr-1 decoy, but not its mutated (scrambled) form, markedly attenuated MCT-induced PH and neointimal formation
Conclusion : This study provides direct evidence of the functional importance of Egr-1 in the MCT-induced PH. Our results indicate that Egr-1 decoy may represent an effective strategy in the treatment of PH.
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