1997 Fiscal Year Final Research Report Summary
Role of vascular angiotensin-generating system in atherosclerosis and acute coronary syndrome : Specifoc role of macrophages and smooth muscle cells
| Project/Area Number |
08670791
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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 | Osaka University |
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Principal Investigator |
RAKUGI Hiromi Osaka University Medical School, Assistant Professor, 医学部, 助手 (20252679)
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| Co-Investigator(Kenkyū-buntansha) |
UEDA Makiko Osaka City University, Associate Professor, 医学部, 助教授 (10137193)
OGIHARA Toshio Osaka University Medical School, Professor, 医学部, 教授 (60107042)
HIGAKI Jituo Osaka University Medical School, Associate Professor, 医学部, 助教授 (70189744)
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| Project Period (FY) |
1996 – 1997
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| Keywords | angiotensin-converting / angiotensin / chymase / ischemic heart disease / immunocytochemistry / macrophages |
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| Research Abstract |
Cardioprotective and vasculoprotective effects of angiotensin-converting enzyme (ACE) inhibitors are well reported. To investigate the role of the renin-angiotensin system in atherogenic diseases, we performed immunocytochemical analyzes using human coronary arteries, molecularbiological analysis using cultured macrophages, and genetic analyzes of cerebral infarction and silent myocardial ischemia.
1. In hypercellular lesion and atheromatous plaque, however, enhanced angiotensin II and ACE expression was found in macrophages and smooth muscle cells. Angiotensin type 1 receptor (AT1) was expressed in the adjacent portion of the cap by the rupture site where consist of contractile smooth muscle cells. Fibrosclerotic plaque showed little or no angiotensin II and ACE within the plaque. Enhanced expression of ACE and angiotensin II were found in culprit lesions of patients with unstable angina. Activation of the renin-angiotensin system in the active lesion of coronary atherosclerosis may pl
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ay an important role in the development of atherosclerosis and acute coronary syndrome. Furthermore, AT1 receptor in the intima may contribute to focal vasoconstriction which triggers plaque rupture.
2. The expression of the components of the renin-angiotensin system were investigated in monocytes (THP-1 : a human monocytic leukemia cell line) and macrophages (differentiated THP-1 by adding of PMA). The expression of AT1 and AT2 was detected in monocytes and increased up to 6.3 and 6.5-fold during the differentiation to macrophages. Renin expression and ACE activity were also enhanced during the differentiation. These results suggest that the renin-angiotensin system function via autocrine-paracrine system in macrophages.
3. Homozygous deletion allele (DD) of the ACE gene is known to be associated higher levels of plasma and tissue ACE activities. We investigated the ACE/DD allele was associated with cerebral infarction but not with cerebral hemorrhage. Silent myocardial ischemia did not show association with polymorphism of the ACE gene. Further studies are required to clarify the mechanism of these association. Less
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