Katrancioglu Nurkay, Karahan Oguz, Kilic Ahmet Turhan, Altun Ahmet, Katrancioglu Ozgur, Polat Zubeyde Akin
Department of Cardiovascular Surgery, Cumhuriyet University School of Medicine, Sivas, Turkey.
Blood Coagul Fibrinolysis. 2012 Apr;23(3):218-21. doi: 10.1097/MBC.0b013e3283504132.
Unfractionated heparin (UFH) and low molecular weight heparins have been used as anticoagulation agents in cardiovascular clinics for decades. However, these molecules also have potent antiangiogenic effects. Whereas, angiogenesis may be the most crucial determinant of the prognosis of cardiovascular diseases, and except some special situation, antiangiogenic effect is not desirable in the most of the cardiovascular disease. In this study, we aimed to compare the antiangiogenic potency of UFH, enoxaparin, and tinzaparin. The antiangiogenic efficacies of UFH, enoxaparin, and tinzaparin were examined in vivo by using the chick chorioallantoic membrane (CAM) model. Twenty fertilized eggs were used for each studied drug. Drug solutions were prepared in 10 and 1 IU/10 μl concentrations. Decreases in the density of the capillaries were assessed and scored. All three drugs showed antiangiogenic effects on the chick CAM at the 10 IU/10 μl concentration. However, the antiangiogenic score of the UFH was significantly higher than that of enoxaparin and tinzaparin at 1 and 10 IU/10 μl concentrations. UFH had stronger and antiangiogenic potential than enoxaparin and tinzaparin. However, tinzaparin showed dose-dependent antiangiogenic effects. We think that an anticoagulant molecule with a less and dose-dependent antiangiogenic effect, as in the case of tinzaparin, may be more desirable in case of cardiovascular disease related with insufficient angiogenesis.
普通肝素（UFH）和低分子肝素作为抗凝剂已在心血管临床应用数十年。然而，这些分子也具有强大的抗血管生成作用。而血管生成可能是心血管疾病预后的最关键决定因素，除了一些特殊情况外，在大多数心血管疾病中抗血管生成作用并非理想。在本研究中，我们旨在比较UFH、依诺肝素和替扎肝素的抗血管生成能力。通过鸡胚绒毛尿囊膜（CAM）模型在体内检测UFH、依诺肝素和替扎肝素的抗血管生成效果。每种研究药物使用20枚受精鸡蛋。药物溶液分别配制成10和1 IU/10 μl的浓度。评估并记录毛细血管密度的降低情况。所有三种药物在10 IU/10 μl浓度时对鸡胚CAM均显示出抗血管生成作用。然而，在1和10 IU/10 μl浓度时，UFH的抗血管生成评分显著高于依诺肝素和替扎肝素。UFH比依诺肝素和替扎肝素具有更强的抗血管生成潜力。然而，替扎肝素表现出剂量依赖性抗血管生成作用。我们认为，对于与血管生成不足相关的心血管疾病，像替扎肝素这种具有较少且剂量依赖性抗血管生成作用的抗凝分子可能更理想。
