| Project/Area Number |
15390248
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 |
OGAWA Hisao Kumamoto University, Department of Cardiovascular Medicine, Graduate School of Medical Sciences, 大学院・医学薬学研究部, 教授 (50177135)
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| Co-Investigator(Kenkyū-buntansha) |
YOSHIMURA Michihiro Kumamoto University, Department of Cardiovascular Medicine, Graduate School of Medical Sciences, 大学院・医学薬学研究部, 助教授 (30264295)
SAKAMOTO Tomohiro Kumamoto University, Department of Cardiovascular Medicine, Graduate School of Medical Sciences, 医学部附属病院, 講師 (00301375)
SUGIYAMA Seigo Kumamoto University, Department of Cardiovascular Medicine, Graduate School of Medical Sciences, 医学部附属病院, 助手 (90274711)
NAKAYAMA Masafumi Kumamoto University, Department of Cardiovascular Medicine, Graduate School of Medical Sciences, 大学院・医学薬学研究部, 助手 (30346986)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥8,600,000 (Direct Cost: ¥8,600,000)
Fiscal Year 2004: ¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 2003: ¥4,600,000 (Direct Cost: ¥4,600,000)
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| Keywords | Acute Coronary Syndrome / Mononuclear Cells / Gene Chip Microarray Analysis / Class A Macrophage Scavenger Receptor / Ontology / Real Time RT-PCR / Directional Coronary Atherectomy / Predictive Marker |
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| Research Abstract |
Morbidity and mortality rates among patients with acute coronary syndrome(ACS) remain to be high. It is difficult to determine which patients will progress satisfactorily for acute coronary syndrome. In this study, we examined gene expression profile of mononuclear cells in the patients in acute and chronic phase of unstable angina to search for the prediction marker of ACS in the circulating mononuclear cells. In the gene chip microarray analysis, the study patients consisted of 2 women with unstable angina without coronary risk factors. We obtained the total RNA of mononuclear cells at the time of admission and three weeks after the admission. We compared the gene expression profile of mononuclear cells between an acute phase and a chronic phase. As a results of microarray, Class A macrophage scavenger receptor(SR-A) was the most strongly increased factor in the acute phase than in the chronic phase among the immune response factors according to the gene ontologic analysis. In larger
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population, we examined SR-A mRNA levels by using real time RT-PCR. The SR-A mRNA levels were 16 times higher in the acute phase than in the chronic phase(p<0.01). Subsequently, we examined the SR-A mRNA levels of circulating mononuclear cells in the consecutive patients who admitted to our institute because of chest pain : 12 control subjects without coronary stenosis, 10 patients with stable angina, and 16 patients with acute coronary syndrome. The SR-A mRNA levels in the control, the stable angina, and the acute coronary syndrome groups were 5.4±1.4,4.5±1.7, and 14.5±2.5, respectively. The SR-A mRNA levels of the peripheral circulating mononuclear cells were highest in the patients with acute coronary syndrome(p<0.01) : there was no significant difference between the control and the stable angina groups. Further, we examined the SR-A mRNA levels of atherosclerotic lesions obtained from directional coronary atherectomies : 11 consecutive patients with unstable angina and 13 consecutive patients with stable angina. The SR-A mRNA levels of the atherosclerotic lesions in the patients with stable angina and with unstable angina were 10.0±6.0 and 38.2±14.5,respectively. The mRNA levels of SR-A of the coronary atheroscrelotic lesions were significantly higher in the patients with unstable angina than in the patients with stable angina(p<0.03). Furthermore, immunohistochemistry revealed that SR-A was abundantly expressed on the macrophages in the atherosclerotic lesions. In conclusion, the SR-A gene expression level increases in the unstable atherosclerotic plaque, and in the peripheral circulating blood in the patients with acute coronary syndrome. Measuring the SR-A gene expression level, even in the peripheral circulating blood provides a marker for acute coronary syndrome. Less
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