An Immunohistochemical Study

This study investigated whether coronary atherosclerosis was different from aortic atherosclerosis in Watanabe heritable hyperlipidemic rabbits. Atherosclerotic lesions were immunohistochemically stained by using a monoclonal antibody for rabbit macrophages (RAM-11) and a monoclonal antibody for muscle actin (HHF35) and were also subjected to conventional staining. The areas of the major lesional components, ie, macrophages, smooth muscle cells, collagen fibers, and extracellular lipid deposits, were measured with a color image analyzer. The percent macrophage area in coronary lesions was significantly lower compared with aortic lesions at all stages (early fatty streak, transitional, and advanced), while the percent smooth muscle cell area and collagen area were significantly higher in early fatty streak lesions of the coronary Epidemiological and clinical studies suggest that the serum cholesterol level is one of the most important risk factors for coronary heart disease. The Watanabe heritable hyperlipidemic (WHHL) rabbit, which develops hypercholesterolemia and atherosclerosis due to a genetic deficiency of low-density lipoprotein receptors," has long been used in studies on atherosclerosis. However, most of these studies have investigated only aortic atherosclerosis, which has been examined in detail by electron microscopy and immunohistochemical techniques."'In contrast, coronary atherosclerosis in WHHL rabbits has not been investigated in detail because both the incidence and severity of coronary atherosclerosis are quite low. Hence, we selectively bred WHHL rabbits to increase the incidence and severity of coronary atherosclerosis. The risk factors for coronary atherosclerosis apparently differ from those for aortic atherosclerosis'; the suppressive or preventive effect of serum cholesterol reduction on coronary atherosclerosis is greater than that on aortic atherosclerosis.' These findings suggest that some qualitative differences may exist between coronary and aortic atherosclerosis. However, no studies have examined the differences between these two types of atherosclerosis. Received November 9, 1993; revision accepted March 2, 1994. From the Institute for Experimental Animals (M.S., T.I., T.Y.), Kobe University School of Medicine, Kobe; the Second Department of Internal Medicine (T.T.), Sanraku Hospital, Tokyo; and the First Department of Pathology (M.U.), Osaka City University Medical School, Osaka, Japan. Correspondence to Masashi Shiomi, PhD, Institute for Experimental Animals, Kobe University School of Medicine, Kusunokicho, Chuo-ku, Kobe 650, Japan. arteries. In addition, the macrophage area/smooth muscle cell area ratio was significantly lower in coronary lesions compared with aortic lesions at all stages. In conclusion, coronary atherosclerosis had a small number of macrophages and was rich in smooth muscle cells, whereas aortic atherosclerosis showed the opposite features. These results suggested that the role of macrophages and smooth muscle cells in the initiation and/or progression of coronary atherosclerosis differs from the role of these cells in aortic atherosclerosis. (Arterioscler Thromb. 1994;14:931-937.)