ACCELERATION OF ATHEROSCLEROTIC LESIONS IN TRANSGENIC MICE WITH HYPERTENSION BY THE ACTIVATED RENIN-ANGIOTENSIN SYSTEM

The present study was designed to investigate the development of ather osclerotic lesions in hypertensive transgenic mice carrying both the h uman renin and angiotensinogen genes (Tsukuba hypertensive mice; THM). THM and C57BL/6J control mice 2 to 3 months of age were fed with eith er an atherogenic or a normal diet for 14 weeks. Although the systolic blood pressure of either strain remained the same regardless of diet, it was significantly higher in THM than in C57BL/6J on both diets. To tal plasma cholesterol concentrations in mice on the atherogenic diet were significantly higher than those in mice fed the normal diet. Lipo protein profiles of cholesterol in THM were fundamentally similar to t hose in C57BL/6J on either the atherogenic or normal diet. Compared wi th controls, however, microscopic analyses revealed accelerated damage of cellular structure in the aortic root in THM fed with the atheroge nic diet. Remarkably, the surface area of atherosclerotic lesion in TH M was shown by quantitative image analysis to be 4 times larger than t hat in C57BL/6J on the same atherogenic diet. These findings suggested that hypertension induced by the activated renin-angiotensin system i s involved in the development of atherosclerotic lesions. Therefore, T HM should be a useful animal model for the study on the pathogenesis o f atherosclerosis.