2004 Fiscal Year Final Research Report Summary
Role of monocyte-derived macrophage and angiotensin in post-infarction left ventricular remodeling
| Project/Area Number |
14570693
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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 | Keio University |
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Principal Investigator |
ANZAI Toshihisa Keio University, Department of Medicine, Assistant Professor, 医学部, 助手 (60232089)
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| Co-Investigator(Kenkyū-buntansha) |
MAEKAWA Yuichiro Keio University, Department of Medicine, Fellow, 医学部, 助手 (90296575)
SUGANO Yasuo Keio University, Department of Medicine, Fellow, 医学部, 助手 (00317124)
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| Project Period (FY) |
2002 – 2004
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| Keywords | myocardial infarction / inflammation / cytokine / remodeling / monocyte / macrophage / heart failure |
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| Research Abstract |
Congestive heart failure is the most common cause of cardiac death after myocardial infarction (MI) and develops during the process of left ventricular (LV) remodeling, which consists of infarct expansion followed by progressive dilatation. In the initial stages of infarct healing, peripheral monocytes infiltrate the necrotic myocardium through the up-regulation of monocyte chemoattractant protein-1 (MCP-1), and differentiate into macrophages. These monocytes and macrophages produce a transforming growth factor-beta1 (TGF-β1), which is a fibrogenic cytokine related to collagen accumulation. Appropriate collagen deposition in the infarcted site is necessary to prevent infarct expansion due to wall stress. Monocytes and macrophages orchestrate the infarct healing process through a complex cascade involving cytokines, growth factors and collagen turnover. A MI model was produced in Wistar rats by ligation of the left coronary artery. Animals after MI were randomized to receive GM-CSF indu
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cer (romurtide 200 μg/kg/day for 7 consecutive days, MI/Ro) or saline (MI/C). Echocardiographic and hemodynamic studies on day 14 revealed increased LV end-diastolic dimension, decreased fractional shortening, elevated LV end-diastolic pressure and decreased LV +dP/dt_<max> in MI/Ro compared with MI/C. Immunoblotting showed that expression of TGF-β1 in the infarcted site on day 3 after MI was decreased in MI/Ro compared with MI/C. In the infarcted site, TGF-β1, collagen type I and type III messenger ribonucleic acid (mRNA) expression on day 3 and collagen content on day 7 were reduced in MI/Ro compared with MI/C, in association with marked infarct expansion. In MI/Ro, monocyte chemoattractant protein-1 mRNA level and the degree of infiltration of monocyte-derived macrophages (ED-1-positive) were greater in the infarcted site on day 7 than those in MI/C. In conclusion, GM-CSF induction by romurtide facilitated infarct expansion in association with the promotion of monocyte recruitment and inappropriate collagen synthesis in the infarcted region during the early phase of MI. Less
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Research Products
(9 results)
