Development of Atherosclerosis on Tsukuba Hypertensive Mice

本研究旨在研究同时携带人肾素和人血管紧张素原基因的高血压转基因小鼠(筑波高血压小鼠，THM)动脉粥样硬化病变的发生发展。THM和C57BL/6J对照组2~3月龄小鼠分别饲喂致动脉粥样硬化饲料和正常饲料14周。虽然THM在两种饲料中的收缩压显著高于C57BL/6J，但在致动脉粥样硬化的饲料中，THM的收缩压在各品系中没有变化。服用致动脉粥样硬化饮食的小鼠的血浆总胆固醇浓度显著高于喂食正常饮食的小鼠。无论是在致动脉粥样硬化的饮食中还是在正常饮食中，THM中胆固醇的脂蛋白谱基本上与C57BL/6J中的相似。然而，与对照组相比，显微镜分析显示，喂饲致动脉粥样硬化饲料的THM主动脉根部细胞结构加速破坏。值得注意的是，定量图像分析显示，在相同的致动脉粥样硬化饮食下，THM的动脉粥样硬化病变表面积是C57BL/6J的4倍。这些结果表明，肾素-血管紧张素系统激活引起的高血压肯定参与了动脉粥样硬化病变的发生发展。THM可作为研究动脉粥样硬化发病机制的一种有用的模型动物。

The present study was designed to investigate the development of atherosclerotic lesions in hypertensive transgenic mice carrying both the human renin and human angiotensinogen genes (Tsukuba hypertensive mice ; THM). THM and C57BL/6J control mice at those ages of 2-3 months were fed with either an atherogenic or a normal diet for 14 weeks. Although systolic blood pressure of THM was significantly higher than that of C57BL/6J on both diets, it did not change on the atherogenic diet in each strain. Total plasma cholesterol concentrations in mice on the atherogenic diet were significantly higher levels than those in mice fed with the normal diet. Lipoprotein profiles of cholesterol in THM were fundamentally similar to those in C57BL/6J either on the atherogenic or normal diet. Compared with controls, however, microscopic analyzes revealed the accelerated damage of cellular structure on aortic root in THM fed with the atherogenic diet. Remarkably, the surface area of atherosclerotic lesion in THM was shown to be four times larger than that in C57BL/6J on the same atherogenic diet by a quantitative image analysis. These findings suggested that hypertension induced by the activated renin-angiotensin system is definitely involved in the development of atherosclerotic lesions. THM should be a useful model animal for the study on the pathogenesis of atherosclerosis.