Development of quantitative analysis method of the atherosclerotic lesions in gene targeted mice

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One of the most reliable methods for the quantitative analysis of atherosclerotic lesions is direct measurement of the lesion size on tissue sections. In this study, we selected the cross-sections through the aortic valve and ascending aorta where the atherosclerosis occurs at very early stage. Using the aortic valve as a marker, the place of the sectioning is easily oriented. In practice, the four slices crossing aortic valve and ascending aorta were selected, and the area of atherosclerosis in each section was measured by the image analysis microscope system.Using this method, it was quantitatively proven that the progress of the atherosclerosis in LDL receptor deficient mice was suppressed in the absence of macrophage scavenger receptor (MSR). Other scavenger receptors than MSR such as CD36, MARCO receptor, and CD68/Macrosialin were considered to concern in the lipid uptake of the macrophages at the remaining lesion. This method was also available for the evaluation of anti-atherosclerosis drugs. The measurement showed that a newly developed antioxidant (BO-653) was effective to reduce the atherosclerotic lesion size in ApoE deficient mice.Though the introduction of the present image analysis microscope system enabled us to carry out the quantitative analysis of the atherosclerosis very conveniently, it has been shown recently that the nature of the atheroma is more concerned to the crisis of the acute coronary syndrome than the degree of stenosis of the artery. Soft atheroma which is rich in macrophages is easy to cause atheroma rupture. From this fact, for the evaluation of the atherosclerosis lesion, it was not sufficient to compare the lesion size only, and it seemed to be important to evaluate the pathological nature of the atheroma itself. This seemed to be the future research subject.