血中薬物濃度モニタリングに基づく医薬品適正使用化に関する研究

取得学位：博士(薬学)，学位授与番号：博乙第101号，学位授与年月日：平成7年9月26日,学位授与年：199

Expression of vascular endothelial growth factor in patients with acute myocardial infarction

AbstractOBJECTIVEThe purpose of this study was to investigate the clinical significance of vascular endothelial growth factor (VEGF) in acute myocardial infarction (AMI). We also examined the involvement of peripheral blood mononuclear cells (PBMCs), which are a possible source of VEGF in AMI.BACKGROUNDVEGF is a potent endothelial cell–specific mitogen and could affect the outcome of AMI.METHODSThirty patients with AMI were used for this study. Serum and PBMCs were isolated from peripheral blood on days 1, 7, 14 and 21 after the onset of AMI. PBMCs were cultured at a density of 5 × 106cells/ml for 24 h. VEGF levels in serum and the culture media were measured by enzyme-linked immunosorbent assay using a specific anti-human VEGF antibody.RESULTSSerum VEGF levels elevated gradually after the onset of AMI and reached a peak on day 14. VEGF levels in the culture medium of PBMCs after incubation for 24 h (PBMC-VEGF) were maximally elevated 7 days after the onset. Maximum serum VEGF levels showed significant positive correlations with maximum creatine phosphokinase (CPK) levels (r = +0.70, p < 0.001), but maximum PBMC-VEGF levels did not correlate with maximum CPK levels. Patients showing improvement in left ventricular systolic function during the course of AMI showed significantly higher PBMC-VEGF levels than patients without improvement.CONCLUSIONSThe extent of myocardial damage contributes to the elevation of serum VEGF levels in AMI. VEGF produced by PBMCs may play an important role in the improvement of left ventricular function by promoting angiogenesis and reendothelialization after AMI