| Co-Investigator(Kenkyū-buntansha) |
IGUCHI Akihisa Nagoya University, Graduate School of Medicine, Professor, 大学院医学系研究科, 教授 (20109763)
CHENG Xianwu Nagoya University, School of Medicine, Research Associate, 医学部, 助手 (30378228)
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| Budget Amount *help |
¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2006: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2005: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Research Abstract |
We developed the murine model of human plaque rupture, which is simple, fast, and highly efficient. The left common carotid arteries of male apolipoprotein E (apoE)-deficient mice were ligated just proximal to their bifurcations. After 4 weeks on a standard diet, the mice received polyethylene cuff placement just proximal to the ligated site. Ligation of the carotid artery in apoE-deficient mice for 4 weeks induced marked intimal hyperplasia, which is a lipid-and collagen-rich lesion that contains a number of macrophages, T lymphocytes, and smooth muscle cells. Subsequently, the cuff placement evoked intraplaque hemorrhage and plaque rupture with fibrin(ogen)-positive luminal thrombus in this region accompanying a decrease in collagen content as well as an increase in leukocytes, and neutrophils, and apoptotic cells in the intima within a few days after cuff placement. MMP-2, MMP-3, MMP-9, MMP-14 mRNA levels in vascular wall increased after cuff placement. In contrast, mRNA level of TIMP-2 decreased. These events observed in this model appear to be analogous to the events in some parts of human plaque rupture. We believe that our model is useful for investigating the pathophysiological mechanisms underlying the development of the vulnerable lesion and plaque rupture of humans. In addition, this plaque rupture model will help us not only to understand the mechanism of human plaque rupture but also to assess various already-known and as-yet unknown agents in the future. In fact, administration of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor prevented the plaque rupture in this model.
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