2004 Fiscal Year Final Research Report Summary
Multidisciplinary approaches to gene therapy of pulmonary hypertension
| Project/Area Number |
14207028
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (A)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Respiratory organ internal medicine
|
|---|
| Research Institution | Chiba University |
|---|
Principal Investigator |
KURIYAMA Takayuki Chiba University, Graduate School of Medicine, Department of Pulmonology, Professor, 大学院・医学研究院, 教授 (20009723)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
TAKIGUCHI Yuichi Chiba University Hospital, Department of Pulmonology, Assistant Professor, 医学部附属病院, 講師 (30272321)
KASAHARA Yasunori Chiba University, Graduate School of Medicine, Department of Pulmonology, Research Associate, 大学院・医学研究院, 助手 (60343092)
TATSUMI Koichiro Chiba University, Graduate School of Medicine, Department of Pulmonology, Associate Professor, 大学院・医学研究院, 助教授 (10207061)
IKEDA Uichi Shinsyu University, Graduate School of Medicine, Department of Cardiology, Professor, 医学部, 循環器内科・教授 (30221063)
SHIRASAWA Takuji Tokyo Metropolitan Institute of Gerontology Molecular Gerontology Group, Group Leader, 分子老化研究グループ, グループ長 (80226323)
|
|---|
| Project Period (FY) |
2002 – 2004
|
| Keywords | Pulmonary hypertension / Gene therapy / Vascular endothelial cell / Vascular smooth muscle cell / Prostacycline / Bosentan / Regeneration |
|---|
| Research Abstract |
To develop novel therapeutic methods for intractable pulmonary hypertension, multidisciplinary researches were conducted and the following findings were obtained.
1.On known genes related to PH. a)Suppression of vascular remodeling : Apoptosis of vascular cells closely related to the vascular remodeling. Different statines worked via distinctively different pathways to induce apoptosis in vascular smooth muscles. Mechanisms of endothelin-1 and angiotensin II on myocardial cells were elucidated. Polymorphism of prostacyclin synthase gene resulted in varied production of 6-keto PG. b)Regeneration of vasculature : In vitro colony forming ability of vascular endothelial cell progenitors were investigated to find that the ability was significantly decreased in patients with pulmonary emphysema and stable coronary insufficiency. It was significantly increased, however, in patients with aortic aneurism. This findings suggested critical roles of the progenitor cells in repairing vascular endothelial damage.
2.On gene introduction methods. a)Development of vector. An AAV vector carrying foreign VEGF gene was successful in recovering organ ischemia in an animal model, b)Establishment of an animal model which enabled gene delivciy specific to the lung : By transfecting a foreign gene to a syngeneic tibroblasts and injecting them to the lung via intra-venous or intra-tracheal routs, the gene expression specific to lung parenchyma was achieved in high levels.
3.Screening of unknown genes related to vascular functions. Cultured human pulmonary arterial endothelial cells and smooth muscle cells were treated by prostacyclin or bosentan, and the gene expressions were exhaustively investigated. Several genes common to both agents responded to the treatment, and were validated by real-time PCR analysis. These findings together would contribute to new strategies for treating intractable pulmonary hypertension.
|
-
-
-
-
-
-
-
[Journal Article] Gene delivery to the lung by means of syngeneic fibroblasts : an experimental model.2003
Author(s)
Suda A, Takiguchi Y, Omori S, Miyazawa H, Sugimoto T, Kurosu K, Tatsumi K, Tanabe N, Kuriyama T, Hiroshima K, Kimura H.
-
Journal Title
Exp Lung Res 29(4)
Pages: 227-241
Description
「研究成果報告書概要(欧文)」より
-
[Journal Article] Oxygen affinity of hemoglobin regulates O2 consumption, metabolism, and physical activity.2003
Author(s)
Shirasawa T, Izumizaki M, Suzuki Y, Ishihara A, Shimizu T, Tamaki M, Huang F, Koizumi K, Iwase M, Sakai H, Tsuchida E, Ueshima K, Inoue H, Koseki H, Senda T, Kuriyama T, Homma I.
-
Journal Title
J Biol Chem 278(7)
Pages: 5035-5043
Description
「研究成果報告書概要(欧文)」より
-
-
-
-
[Journal Article] Incidence and clinical characteristics of chronic pulmonary thromboembolism in Japan compared with acute pulmonary thromboembolism : results of a multicenter registry of the Japanese Society of Pulmonary Embolism Research.2002
Author(s)
Nakamura M, Okada O, Sakuma M, Nakanishi N, Miyahara Y, Yamada N, Fujioka H, Kuriyama T, Kunieda T, Sugimoto T, Nakano T.
-
Journal Title
Circ J 66(3)
Pages: 257-260
Description
「研究成果報告書概要(欧文)」より
