| Project/Area Number |
07670793
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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 |
Circulatory organs internal medicine
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| Research Institution | Kumamoto University |
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Principal Investigator |
KUGIYAMA Kiyotaka Kumamoto University School of medicine, Division of Cardiology, Assistant Professor, 医学部, 講師 (00225129)
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| Project Period (FY) |
1995 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1996: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1995: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Keywords | Atherosclerosis / Lysolecithin / Endothelial Cells / Protein Kinase C / Gene Transcription / Phospholipase A2 / phospholipase A_2 |
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| Research Abstract |
Lysolecithin (lysoPC), which abundantly exists in atherosclerotic arterial walls, has been shown to alter various endothelial functions and induce several endothelial genes expressed in atherosclerotic arterial walls and inflammatory sites. To determine whether lysoPC could modulate endothelial NF-kB activation, we incubated cultured human umbilical vein endothelial cells (HUVECs) with lysoPC and examined the NF-kB binding activity in the nuclear extracts of HUVECs by electrophoretic mobility shift assays. The experiments showed that lysoPC regulates endothelial NF-kB activity in a biphasic manner dependent on its concentration and incubation time, and the endothelial protein kinase C (PKC) activation may in part be involved in the lysoPC-induced NF-kB activation.
Concentrations of lysolecithin are greatly increased in atherosclerotic arterial walls. There are at least two sources of lysolecithin found in atherosclerotic arterial walls. One souce is oxidized low-density lipoprotein (Ox-
… More
LDL), which accumulates in atherosclerotic arterial walls. LDL oxidation is associated with the hydrolysis of lecithin to lysoPC by the action of an intrinsic LDL-associated phospholipase A2 (PLA2). Thus, we further examined the role of secretary type II PLA2 in the pathophysiology of atherosclerotic coronary artery disease. The study with radioimmunoassay of PLA2 in peripheral circulation showed that plasma levels of type II PLA2 were increased in the peripheral circulation at aortic root, coronary sinus and femoral vein in effort angina and old myocardial infarction. The level of PLA2 was also increased in peripheral circulation in patients with acute myocardial infarction with a peak at 3th day after the onset of the disease.
These results indicate that lysoPC could modulate expression of some endothelial genes through regulating the activation of transcription factor of NF-kB in atherosclerotic arteries and PLA2 may play an important role in the pathophysiology of atherosclerotic coronary artery disease. Less
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