2001 Fiscal Year Final Research Report Summary
Roles of prostanoids in cardiovascularsystem revealed from studies using knockout mice
| Project/Area Number |
11470020
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General pharmacology
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| Research Institution | Asahikawa Medical College |
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Principal Investigator |
USHIKUBI Fumitaka Asahikawa Medical College, Pharmacology, Professor, 医学部, 教授 (50243035)
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| Co-Investigator(Kenkyū-buntansha) |
HARA Akiyoshi Asahikavva Medical College, Pharmacology, Associate Professor, 医学部, 助教授 (90164988)
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| Project Period (FY) |
1999 – 2000
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| Keywords | prostanoids / prostaglandin / thromboxane / knockout mice / prostanoid receptor / cardiovascular system / platelets / ischemia-reperfusion |
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| Research Abstract |
The prostanoids are lipid mediators showing variable effects on many organs in the body including the cardiovascular system. Their roles in the system, however, have been largely unknown. We attempted to clarify these roles using mice lacking the prostanoids receptors individually. We first established variable methods for the analysis. These include in vivo models such as for cardiac hypertrophy, thromboembolism, vascular remodeling and renovascular hypertension, and in vitro systems for culture of vascular smooth muscle cells, cultures of cardiomyocytes from fetal or adult mice, platelet aggregation and vascular tone. We next examined the roles of the prostanoids using the established methods and knockout mice, Prostaglandin (PG)l_2 was found to be a potent mediator to protect the cardiomyocytes from ischemia-reperfusion injury. PGE_2 potentiated the platelet activation induced by other platelet stimulants, such as thromboxane A_2 and ADP. Furthermore, this potentiating effect on the platelets was verified to be important in both hemostasis and thromboembolism. Other roles of the prostanoids in the cardiovascular system would be clarified in near future, because several interesting results have been already obtained in the present project. They include the roles in various pathological conditions such as cardiac hypertrophy, vascular remodeling and renovascular hypertension
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