| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2005: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Research Abstract |
Background : Recent studied indicates that therapeutic angiogenesis with vascular endothelial cell growth factor-A (VEGF-A) is not always effective in acute myocardial infarction (MI), mainly because it induces only immature vasculature. Placental growth factor (P1GF), a member of VEGF family, is different from VEGF-A in receptor specificity. P1GF specifically binds to VEGF receptor-1 (flt-1), though VEGF-A binds to both VEGF receptors 1 and 2. Recent our clinical work demonstrates that P1GF is rapidly produced within infarct myocardial tissue, and the plasma level of P1GF is positively correlated with number of monocytes and CD34 positive cells, and improvement of left ventricular function. However, therapeutic effects of P1GF on MI are not understood.
Methods and Results : One day before ligation of coronary artery, recombinant human P1GF (rhP1GF) (10μg) was infused into the peritoneal cavity of C57BL/6 mice through subcutaneously implanted osmotic mini pump until 2 days after the lig
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ation. After 28 days, survival rate was significantly higher in rhP1GF-treated Group (70.0%) than PBS-Group (33.3%) (p<0.05). Seven days after MI, the infarct area, stained by 1.5% TTC (2,3,5-triphenyltetrazolium chloride), was smaller in rhP1GF-treated group (4.25±2.04mm^2) than PBS-group (5.95±1.54mm^2), and it indicates exogenous P1GF suppressed cardiac remodeling. Echocardiography also revealed that left ventricular diastolic diameter was decreased (rhP1GF: 4.50±0.46mm, PBS: 5.14±0.38mm p<0.01), and ejection fraction was increased in rhP1GF-treated group (rhP1GF: 40.6±9.17%, PBS: 25.7±7.23% p<0.01). Histological analysis showed that both CD31-positive vascular endothelial cells (rhP1GF: 644.6±90.54/mm^2, PBS: 459.0±73.89/mm^2 p<0.01) and a-smooth muscle actin-positive vessels (rhP1GF: 31.6±7.20/mm^2, PBS: 23.5±7.41/mm^2 p<0.01) was increased at infarct area, and it implied that both angiogenesis and arteriogenesis contributes to the improvement of cardiac function.
Conclusion : rhP1GF-treatment preserved left ventricular function and inhibited post-infarct remodeling by enhancing neovascularization and arteriogenesis, through which rhP1GF-treatment improved survival rate after myocardial infarction. Less
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