| Project/Area Number |
14570687
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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 | Shinshu University Graduate School of Medicine (2003)
Jichi Medical University (2002) |
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Principal Investigator |
TAKAHASHI Masafumi Shinshu University Graduate School of Medicine, Department of Organ Regeneration, Associate Professor, 大学院・医学研究科, 助教授 (40296108)
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| Co-Investigator(Kenkyū-buntansha) |
KOBAYASHI Eiji Shinshu University Graduate School of Medicine, Jichi Medical School, Professor, 医学部, 教授 (00245044)
OSE Hirohiko Shinshu University Graduate School of Medicine, Department of Organ Regeneration, Assistant, 大学院・医学研究科, 助手 (10324253)
IKEDA Uichi Shinshu University Graduate School of Medicine, Department of Organ Regeneration, Professor, 大学院・医学研究科, 教授 (30221063)
島田 和幸 自治医科大学, 医学部, 教授 (90145128)
袴田 陽二 自治医科大学, 医学部, 講師 (00218380)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2003: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2002: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | Cytokine / Atherosclerosis / Ischemic heart disease / Oxidative stress / Inflammation / Cardiomyocyte |
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| Research Abstract |
Increasing evidence indicates that inflammatory responses play an important role in the pathphysiology of atherosclerosis and ischemic heart diseases. In the present study, we explored the expression and role of macrophage migration inhibitory factor (MIF) that is regulator for inflammatory responses in cardiovascular diseases such as atherosclerosis and ischemic heart diseases.
1.Expression of MIF in cardiovascular cells
In vitro study using cultured rat neonatal cardiomyocytes demonstrated that significant amounts of MIF were produced in response to oxidative stress. This MIF production was mediated through calcium-insensitive and phorbol ester-insensitive protein kinase C (PKC) pathway, suggesting that oxidative stress induced MIF production is mediated by an atypical PKC isoform. The experiments using dominant negative-PKC isoform further suggest that PKC zeta is involved in this pathway.
2.Expression of MIF in animal models of cardiac diseases
We examined neointima formation and perivascular inflammatory cell infiltration induced by a cuff replacement model in MIF-transgenic and MIF knockout mice. Unfortunately, we observed no significant differences of atherosclerosis formation among control B6 mice, MIF-transgenic mice, and MIF-knockout mice.
3.Role of MIF in patients with acute myocardial infarction
In patients with acute myocardial infarction (AMI), plasma MIF levels were markedly elevated during acute stages of AMI, whereas MIF levels in peripheral blood mononuclear cells increased during subacute stages, suggesting that the MIF production in AMI differ between the acute and subacute stages of AMI by the myocardium and inflammatory blood cells, respectively.
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