| Budget Amount *help |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2004: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2003: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Research Abstract |
Placental growth factor(PlGF), a specific ligand for fit-1, is known to stimulate the recruitment of monocyte from bone marrow into the injured tissue, and seems to enhance wound healing processes by activating monocyte and inducing arteriogenesis. However, clinical significance of PlGF in myocardial infarction(MI) has not been understood. This study investigated expression pattern of PlGF and the impact of PlGF on the clinical course in patients and mouse models of acute MI. Methods and Results : Human study : Fifty five patients with acute MI and 43 controls were enrolled. Blood sampling was performed from peripheral vein, ostium of coronary artery(CA), and coronary sinus(CS), before and after recanalization(RC) of occluded CA. Plasma levels of PlGF were measured by ELISA. Transcardiac gradient of plasma PlGF ([CS]-[CA]) just after RC of the occluded CA was significantly higher than the value before RC (14.1±10.6 vs, 0.0±1.1pg/ml p<0.01), indicating cardiac production and release of
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PlGF from infarct heart. Peak plasma PlGF levels (3.2±1.1 days) were significantly higher than those in control subjects (35.1±26.5 pg/ml vs 13.4±5.7 pg/ml, p<0.001). Peak plasma PlGF levels positively correlated with peak peripheral monocyte counts during acute phase of MI (r=0.42,p<0.005), although they did not correlated with age, gender, time to reperfusion, or peak CK-MB. Furthermore, multiple regression analysis revealed that PlGF was the strongest independent predictor for the restoration of left ventricular ejection fraction examined at 6-month follow-up study (p=0.0098). Mouse study : In mouse models of MI, tissue PlGF mRNA expression was increased 26.6 fold (p<0.001) compared with sham operated heart. Immunohistochemical staining showed that PlGF protein was over-expressed mainly in endothelial cells of coronary artery in the infarct region, but scarcely in non-infarct region. Conclusion : PlGF is rapidly produced in the infarct myocardial tissue, especially endothelial cells of coronary artery in infarct region during acute phase of MI, and over-expressed PlGF seems to be involved in the improvement of left ventricular function in chronic phase probably by recruiting monocyte from bone marrow. Less
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