| Project/Area Number |
05404022
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| Research Category |
Grant-in-Aid for General Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
Human pathology
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| Research Institution | Keio University |
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Principal Investigator |
HOSODA Yasuhiro Department of Pathology, School of Medicine, Keio Univ., Professor, 医学部, 教授 (90051218)
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| Co-Investigator(Kenkyū-buntansha) |
KISHIDA Yukiko Department of Pathology, School of Medicine, Keio Univ., Instructor, 医学部, 助手 (40204854)
KAMEYAMA Kaori Department of Pathology, School of Medicine, Keio Univ., Instructor, 医学部, 助手 (10245467)
IKEDA Eiji Department of Pathology, School of Medicine, Keio Univ., Instructor, 医学部, 助手 (30232177)
KURAMOCHI Shigeru Department of Pathology, School of Medicine, Keio Univ., Assistant Professo, 医学部, 講師 (70137991)
HATA Jun-ichi Department of Pathology, School of Medicine, Keio Univ., Professor, 医学部, 教授 (90051614)
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| Project Period (FY) |
1993 – 1995
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| Project Status |
Completed (Fiscal Year 1995)
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| Budget Amount *help |
¥33,800,000 (Direct Cost: ¥33,800,000)
Fiscal Year 1995: ¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1994: ¥6,400,000 (Direct Cost: ¥6,400,000)
Fiscal Year 1993: ¥25,100,000 (Direct Cost: ¥25,100,000)
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| Keywords | pulmonary hypertension / plexiform lesion / collagen vascular disease / recurrent pulmonary thrombosis / monocrotaline / serotonin / DV-7028 / endothelial cell / 内皮細胞障害 / EDRF / PGI_2 / モノクロタリン / トロポエラスチン / alternative splicing / 肺区血圧症 / 肺動脈 / Plexiform lesion / エンドセリン‐1 / 膠状病変 / 反復性肺血栓塞栓症 |
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| Research Abstract |
1) We have conducted an etiological study concerning autopsy cases of pulmonary hypertension (PH) in our country and found that the incidence of so-called plexogenic types was high. This is in sharp contrast to western countries. In addition, among collagen vascular disease-related PH,the CREST syndrome, a variant of scleroderma, is said to be frequent in European countries and the U.S,but we have found PH more often associated with SLE and MCTD.
2) Through histopathological studies, we found that the degree of medial thickening of the muscular pulmonary arteries and intimal thickening, plexiform lesions and thrombosis were useful markers for the evaluation of PH,while othe lesions such a hemosiderosis were not necessaryly prevalent. We surmised that arteritis of the pulmonary artery seen in collagen vascular disease-related PH is not necessarily secondary to the PH,and its relationship to the underlying disease should be considered.
3) Recurrent pulmonary thrombosis seems to be a rare disease here, but the existence of a case considered to be microthrombotic was pointed out.
4) Using the model of monocrotaline (MCT) -induced PH,the pathogenesis of PH was investigated. Scrutinizing the actions of serotonin, DV-7028, a 5-HT_2 receptor antagonist, was used to reveal that serotonin derived from platelets adherent to injured endothelial cells playd an important role in MCT-induced PH.We think that the activities of platelets and serotonin fully deserve to be studied in naturally occurring PH as well. EDRF,PGI_2 were also discovered to be active, so that multiple factors were understood to be involved in the genesis and progression of PH.
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