Bougioukas Ioannis, Didilis Vassilios, Ypsilantis Petros, Giatromanolaki Alexandra, Sivridis Efthimios, Lialiaris Theodoros, Mikroulis Dimitrios, Simopoulos Constantinos, Bougioukas Georgios
Department of Cardiothoracic Surgery, School of Medicine, Democritus University of Thrace, University General Hospital of Alexandroupolis, Dragana, 68 100 Alexandroupolis, Greece.
Cardiovasc Pathol. 2007 Mar-Apr;16(2):63-8. doi: 10.1016/j.carpath.2006.08.006.
Myocardial angiogenesis after the systemic administration of basic fibroblast growth factor or vascular endothelial growth factor at high therapeutic doses has been implicated in the occurrence of side effects that may undermine their safety. The aim of this study was to investigate the angiogenic effects of the intramyocardial administration of recombinant human basic fibroblast growth factor or vascular endothelial growth factor protein, at low doses, in the infarcted rabbit myocardium.
Twenty-five New Zealand White rabbits were divided into five groups (n=5) and subjected to coronary artery ligation after lateral thoracotomy, inducing acute myocardial infarction. Five minutes later, the following substances were injected intramyocardially into the infarcted area: (a) normal saline (controls); (b) 6.25 or 12.5 mug of recombinant human basic fibroblast growth factor protein (basic fibroblast growth factor-1 group or basic fibroblast growth factor-2 group); or (c) 5 or 10 microg of recombinant human vascular endothelial growth factor 165 protein (vascular endothelial growth factor-1 group or vascular endothelial growth factor-2 group). On the 21st postoperative day, the animals were euthanized, and their hearts were subjected to histopathological examination and immunohistochemical assessment of vascular density in the infarcted area. The alkaline phosphatase anti-alkaline phosphatase procedure and the primary monoclonal antibody JC70 were used. Histopathological examination confirmed the induction of myocardial infarction. Vascular density was significantly increased (P<.004) in all treatment groups (in mean+/-S.E. vessels/x 200 optical field: basic fibroblast growth factor-1: 85.8+/-10.9; basic fibroblast growth factor-2: 76.6+/-3.7; vascular endothelial growth factor-1: 73.4+/-3.2; vascular endothelial growth factor-2: 89.5+/-5.2) compared to that in controls (58.9+/-4.9 vessels/x 200 optical field). Vascular density in the vascular endothelial growth factor-2 group was significantly higher than that in the vascular endothelial growth factor-1 group (P<.001).
Low doses of recombinant human basic fibroblast growth factor or vascular endothelial growth factor protein, when administered intramyocardially, stimulate angiogenesis in the infarcted myocardium.
全身给予高治疗剂量的碱性成纤维细胞生长因子或血管内皮生长因子后发生的心肌血管生成与可能损害其安全性的副作用有关。本研究的目的是探讨低剂量重组人碱性成纤维细胞生长因子或血管内皮生长因子蛋白心肌内注射对梗死兔心肌的血管生成作用。
25只新西兰白兔分为5组（每组n = 5），经左胸开胸后进行冠状动脉结扎，诱导急性心肌梗死。5分钟后，将以下物质心肌内注射到梗死区域：（a）生理盐水（对照组）；（b）6.25或12.5μg重组人碱性成纤维细胞生长因子蛋白（碱性成纤维细胞生长因子-1组或碱性成纤维细胞生长因子-2组）；或（c）5或10μg重组人血管内皮生长因子165蛋白（血管内皮生长因子-1组或血管内皮生长因子-2组）。术后第21天，处死动物，对其心脏进行组织病理学检查和梗死区域血管密度的免疫组化评估。采用碱性磷酸酶抗碱性磷酸酶法和一抗单克隆抗体JC70。组织病理学检查证实了心肌梗死的诱导。与对照组（每200视野58.9±4.9条血管）相比，所有治疗组的血管密度均显著增加（P<0.004）（平均±标准误每200视野血管数：碱性成纤维细胞生长因子-1组：85.8±10.9；碱性成纤维细胞生长因子-2组：76.6±3.7；血管内皮生长因子-1组：73.4±3.2；血管内皮生长因子-2组：89.5±5.2）。血管内皮生长因子-2组的血管密度显著高于血管内皮生长因子-1组（P<0.001）。
低剂量重组人碱性成纤维细胞生长因子或血管内皮生长因子蛋白心肌内注射可刺激梗死心肌血管生成。
