Torry R J, Labarrere C A, Torry D S, Holt V J, Faulk W P
Center for Reproduction and Transplantation Immunology, Methodist Hospital of Indiana, Indianapolis 46202, USA.
Transplantation. 1995 Dec 27;60(12):1451-7. doi: 10.1097/00007890-199560120-00014.
Vascular endothelial growth factor (VEGF) is an endothelial cell-specific mitogen thought to play an important role in coronary collateral vessel formation. We used immunocytochemistry to determine VEGF expression in biopsies (n = 283) of transplanted human hearts (n = 109) with and without microvascular fibrin. Measures of vascular fibrin, alpha 2 plasmin-inhibitor (a2Pl), macrophages, neutrophils, and serum cardiac troponin T titers were used to evaluate myocardial damage. Antibody to T lymphocytes was used to evaluate cellular rejection, and HLA-DR, ICAM-1, and PAL-E antibodies were used to assess endothelial cell activation and phenotypic changes in the microcirculation. No VEGF immunoreactivity was detected in control donor hearts without fibrin, but the proportion of biopsies demonstrating VEGF immunoreactivity increased significantly in allografts with increasing fibrin and a2PI reactivity (P = 0.0001). VEGF immunoreactivity was confined to areas of fibrin deposition and was associated with infiltrates of macrophages and neutrophils (P < 0.0001), but not with T cells (P = 0.10). Biopsies with fibrin/VEGF reactivity were associated with increased capillary endothelial cell HLA-DR, ICAM-1, and PAL-E reactivity. In a subset of patients, serum cardiac troponin-T values were greater in patients with VEGF-positive (n = 21) than VEGF-negative (n = 19) biopsies (P = 0.05). Nested RT-PCR demonstrated that biopsies with and without fibrin/VEGF immunoreactivities expressed VEGF121, VEGF165, and VEGF189 variants, with VEGF165 being the dominate variant. These results indicate that endogenous VEGF is expressed locally following vascular thrombosis and myocardial cell damage, and that VEGF expression may be related to endothelial cell activation and phenotypic changes found in the microcirculation of cardiac allografts.
血管内皮生长因子（VEGF）是一种内皮细胞特异性促有丝分裂原，被认为在冠状动脉侧支血管形成中起重要作用。我们采用免疫细胞化学方法，测定了伴有和不伴有微血管纤维蛋白的移植人心脏活检组织（n = 283）（心脏数量n = 109）中的VEGF表达。采用血管纤维蛋白、α2纤溶酶抑制剂（a2Pl）、巨噬细胞、中性粒细胞以及血清心肌肌钙蛋白T滴度的检测指标来评估心肌损伤。采用T淋巴细胞抗体评估细胞排斥反应，采用HLA - DR、ICAM - 1和PAL - E抗体评估内皮细胞活化及微循环中的表型变化。在无纤维蛋白的对照供体心脏中未检测到VEGF免疫反应性，但在同种异体移植心脏中，随着纤维蛋白和a2PI反应性增加，显示VEGF免疫反应性的活检组织比例显著升高（P = 0.0001）。VEGF免疫反应性局限于纤维蛋白沉积区域，并与巨噬细胞和中性粒细胞浸润相关（P < 0.0001），但与T细胞无关（P = 0.10）。具有纤维蛋白/VEGF反应性的活检组织与毛细血管内皮细胞HLA - DR、ICAM - 1和PAL - E反应性增加相关。在一部分患者中，VEGF阳性活检组织（n = 21）的患者血清心肌肌钙蛋白 - T值高于VEGF阴性活检组织（n = 19）的患者（P = 0.05）。巢式逆转录聚合酶链反应（Nested RT - PCR）表明，有和没有纤维蛋白/VEGF免疫反应性的活检组织均表达VEGF121、VEGF165和VEGF189变体，其中VEGF165是主要变体。这些结果表明，内源性VEGF在血管血栓形成和心肌细胞损伤后在局部表达，并且VEGF表达可能与心脏同种异体移植微循环中发现的内皮细胞活化和表型变化有关。
