2003 Fiscal Year Final Research Report Summary
Studies onfanction of prostacyclin and thromboxane in vascular disorders
| Project/Area Number |
14570115
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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 |
General medical chemistry
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| Research Institution | National Cardiovascular Center Research Institute |
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Principal Investigator |
YOKOYAMA Chieko National Cardiovascular Center Research Institute, Department Pharmacology, Laboratory Chief, 薬理部, 室長 (90200914)
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| Co-Investigator(Kenkyū-buntansha) |
NARABA Hiroaki National Cardiovascular Center Research Institute, Department Pharmacology, Research Staff, 薬理部, 室員 (90296517)
TOSHIHISA Hatae National Cardiovascular Center Research Institute, Department Pharmacology, Research Staff, 薬理部, 室員 (10251026)
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| Project Period (FY) |
2002 – 2003
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| Keywords | prostacyclin / prostaglandin / prostacyclin synthase / knockout mice / vascular endothelial cells / PPAR-delta / kidney / arteriosclerosis |
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| Research Abstract |
Prostacyclin (PGI_2) and thromboxane (TX) are lipid mediators derived from arachidonic acid and play important role for homeostasis of vascular system. However, their detail mechanism of function is still unclear. In order to study the role of PGI_2, TX and prostaglandin (PG) E_2 in the cardiovascular diseases, the genetically modified mice and the overexpressing cells of these biosynthetic enzymes. The obtained results are as follows.
1.PGI_2-deficient (PGID) mice generated by genetic disruption of PGI_2 synthase gene developed vascular disorders including arteriosclerosis in the kidneys and aorta. In PGID mice, thromboxane and PGE_2 levels in plasma and tissues rose compared with those of wild-type mice. The increase in mRNA revels of pro-inflammatory cytokines and/or those related genes was observed in addition to the elevated expression of genes for extracellular matrix by gene chip analysis.
2.The overexpression of PGI_2 synthase in endothelial cells induced a certain anti-inflammatory cytokine. Five repeats of the consensus sequence of PPAAR responsive element were found in the 5' upstream region of this cytokine gene and the PGI_2-PPAR-delta signaling pathway was involved in the induction of the cytokine.
3.Gene structure and transcriptional regulation of membrane associated PGE synthase were analyzed and a transcriptional factor, Egr-1 was essential for the expression of the enzyme.
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