Development of Atherosclerosis on Tsukuba Hypertensive Mice

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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.