Jain Manish, Frobert Aurélien, Valentin Jérémy, Cook Stéphane, Giraud Marie-Noëlle
Cardiology, Department of Medicine, University of Fribourg.
Cardiology, Department of Medicine, University of Fribourg;
J Vis Exp. 2017 Oct 3(128):55295. doi: 10.3791/55295.
Acute coronary syndrome resulting from coronary occlusion following atherosclerotic plaque development and rupture is the leading cause of death in the industrialized world. New Zealand White (NZW) rabbits are widely used as an animal model for the study of atherosclerosis. They develop spontaneous lesions when fed with atherogenic diet; however, this requires long time of 4 - 8 months. To further enhance and accelerate atherogenesis, a combination of atherogenic diet and mechanical endothelial injury is often employed. The presented procedure for inducing atherosclerotic plaques in rabbits uses a balloon catheter to disrupt the endothelium in the left iliac artery of NZW rabbits fed with atherogenic diet. Such mechanical damage caused by the balloon catheter induces a chain of inflammatory reactions initiating neointimal lipid accumulation in a time dependent fashion. Atherosclerotic plaque following balloon injury show neointimal thickening with extensive lipid infiltration, high smooth muscle cell content and presence of macrophage derived foam cells. This technique is simple, reproducible and produces plaque of controlled length within the iliac artery. The whole procedure is completed within 20 - 30 min. The procedure is safe with low mortality and also offers high success in obtaining substantial intimal lesions. The procedure of balloon catheter induced arterial injury results in atherosclerosis within two weeks. This model can be used for investigating the disease pathology, diagnostic imaging and to evaluate new therapeutic strategies.
动脉粥样硬化斑块形成和破裂后冠状动脉闭塞导致的急性冠状动脉综合征是工业化国家的主要死因。新西兰白兔(NZW)被广泛用作动脉粥样硬化研究的动物模型。喂食致动脉粥样硬化饮食时,它们会自发形成病变;然而,这需要4至8个月的长时间。为了进一步增强和加速动脉粥样硬化的形成,通常采用致动脉粥样硬化饮食和机械性内皮损伤相结合的方法。本文介绍的在兔子中诱导动脉粥样硬化斑块的方法是,使用球囊导管破坏喂食致动脉粥样硬化饮食的NZW兔子左髂动脉的内皮。球囊导管造成的这种机械损伤会引发一系列炎症反应,以时间依赖的方式引发内膜脂质积聚。球囊损伤后的动脉粥样硬化斑块表现为内膜增厚,伴有广泛的脂质浸润、高平滑肌细胞含量以及巨噬细胞衍生的泡沫细胞。该技术简单、可重复,并且能在髂动脉内产生长度可控的斑块。整个过程在20至30分钟内完成。该过程安全,死亡率低,并且在获得大量内膜病变方面成功率也很高。球囊导管诱导的动脉损伤过程在两周内会导致动脉粥样硬化。该模型可用于研究疾病病理、诊断成像以及评估新的治疗策略。