2014 Fiscal Year Final Research Report
The Role of Prostaglandin E2 Receptor EP4 Signaling in the Vascular Smooth Muscles
| Project/Area Number |
25860614
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Cardiovascular medicine
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| Research Institution | Yokohama City University |
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Principal Investigator |
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| Project Period (FY) |
2013-04-01 – 2015-03-31
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| Keywords | EP4 / 大動脈瘤 / 血管平滑筋 / MMP |
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| Outline of Final Research Achievements |
Elasticity contributes to mechanical properties of the arteries and loss of elastic properties exacerbates aortic aneurysms (AA). It is well known that prostaglandin E2 (PGE2) synthesis is enhanced in AA. We have demonstrated that the PGE2 receptor EP4 was abundantly expressed in smooth muscle cells (SMCs) from human AA tissues. We examined whether PGE2-EP4 signaling in SMCs decreases elasticity in the aorta. We generated mice with vascular smooth muscle-specific overexpression of human EP4 using the Cre-loxP system. After angiotensin II (ATII) infusion, however, the aorta of EP4TG were deformed and enlarged to a greater degree than that of EP4NTG. Further, elasicity was decreased in EP4TG than in EP4NTG. MMP-2 activity of EP4TG is higher than that of EP4NTG in the basal condition by gelatin zymography. MMP-9 activity was also abundant in EP4TG under ATII treatment. EP4 signaling in SMCs is suggested to be decreased aortic elasticity by promoting the degradation of elastic fibers.
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| Free Research Field |
血管生物学
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