| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2013: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Outline of Final Research Achievements |
The diverse clinical characteristics of obesity illustrate the complexity of this disease, involving the dysregulation of several metabolic pathways and multiple genetic targets. To understand the effect of obesity on the pathophysiology of myocardial infarction, we used high fat died (HFD) induced obesity mice with left descending artery ligation (HFD-MI). Compared with mice fed normal chow diet (NC) induced myocardial infarction (NC-MI), the prognosis of HFD-MI is worse and heart failure is exacerbated. Microarray analysis 24 hours after MI or sham operation shows that the expression level of plasminogen activator inhibitor-1 (PAI-1) is elevated in both the liver and the adipose tissue. Treatment with PAI-1 inhibitor improved the prognosis of HFD-MI. Cardiac remodeling and heart failure was significantly attenuated in PAI-1 hetero-knockout mouse with HFD than wild type littermate. In conclusion, we suggest PAI-1 is the therapeutic target of myocardial infarction with obesity.
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