Experimental models of thrombosis and atherosclerosis.
Experimental models of thrombosis and atherosclerosis.
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DOI：
10.2515/therapie:2006069
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发表时间：
2006-09
期刊：
影响因子：
2.6
通讯作者：
T. Verbeuren
中科院分区：
文献类型：
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作者：
T. Verbeuren
动脉粥样硬化血栓形成是一种复杂的疾病，包括两种不同的病理：动脉粥样硬化，动脉壁中斑块形成的过程和血栓形成，主要在破裂的动脉粥样硬化病变部位形成血凝块。这两种病理的动物模型有助于了解其病因及其演变，并用于评价新治疗方法的疗效。已经描述了许多用于研究静脉和动脉血栓形成的模型。因此，在大鼠中，经常使用由损伤/淤滞诱导的静脉血栓形成，例如在腔静脉中，以及通过血管壁损伤诱导的动脉血栓形成。直接（血栓重量）或间接（血流减少）测量所产生的血凝块形成。为了检查冠状动脉血栓形成，已经在大型动物如狗和猪中开发了更复杂的模型;原理总是导致血栓形成的动脉病变。TP-受体拮抗剂terutroban（S 18886）对不同血栓形成模型的影响已得到评价，这使得可以得出该药物强大的抗血栓形成作用的结论，并有助于其进入临床开发。在过去，最常用的动脉粥样硬化模型是高胆固醇血症兔;斑块形成及其对血管内皮功能的影响在此模型中已被大量研究。最近引入了动脉粥样硬化的基因工程小鼠模型，现在主要研究它们以表征疾病和评估新药。主要使用的两种模型是ApoE（-/-）和LDL受体（-/-）小鼠。用terutroban进行的研究表明，这种TP受体拮抗剂可防止小鼠和兔模型中的病变形成，这说明了其有趣的抗动脉粥样硬化特性，并证明了内皮TP受体在动脉粥样硬化形成中所起的作用。总之，研究动脉粥样硬化和血栓形成的实验模型已经开发出来，并用于研究动脉粥样硬化血栓形成疾病的病因和演变。他们也有很大的价值，以预测抗血栓形成和/或抗动脉粥样硬化的新物质，如特鲁曲班，这可能成为新的治疗这种复杂的心血管疾病的性质。
Atherothrombosis is a complex disease which includes two different pathologies: atherosclerosis, the process of plaque formation in the arterial wall and thrombosis, the formation of a blood clot mostly at the site of a ruptured atherosclerotic lesion. Animal models for both pathologies have been useful to understand their aetiology and their evolution and they were used to evaluate the efficacy of new treatments. Numerous models to study venous and arterial thrombosis have been described. Thus in the rat, venous thrombosis induced by lesion/stasis, e.g. in the vena cava, and arterial thrombosis by lesioning of the vessel wall are frequently used. The resulting blood clot formation is measured either directly (weight of the thrombus) or indirectly (reduction in blood flow). More complex models have been developed in large animals such as dogs and pigs in order to examine coronary thrombosis; the principle always being the arterial lesion that causes the thrombus formation. The effect of the TP-receptor antagonist terutroban (S 18886) on different thrombosis models has been evaluated and this has allowed to conclude on the powerful anti-thrombotic effects of this agent and has contributed to its progression into clinical development. In the past the most frequently used model of atherosclerosis was the hypercholesterolemic rabbit; both plaque formation and its consequences on vascular, endothelial, function have been largely studied in this model. More recently genetically engineered mouse models of atherosclerosis have been introduced and they are now largely studied to characterize the disease and to evaluate new drugs. The two models mostly used are the ApoE(-/-) and the LDL receptor(-/-) mice. Studies with terutroban have illustrated that this TP-receptor antagonist prevents lesion formation in mouse and rabbit models illustrating its interesting anti-atherosclerotic properties and demonstrating the role played by endothelial TP-receptors in atherogenesis. In conclusion, experimental models to study atherosclerosis and thrombosis have been developed and used to study the etiology and the evolution of atherothrombotic disease. They have also been of great value to predict anti-thrombotic and/or anti-atherosclerotic properties of new substances such as terutroban, that may become novel treatments for this complex cardiovascular disease.