Natural history of atherosclerosis and hyperlipidemia in heterozygous WHHL (WHHL-Hh) rabbits. II. Morphologic evaluation of spontaneously occurring aortic and coronary lesions.

This study evaluated the morphologic appearance of spontaneous aortic and coronary atherosclerotic lesions in 21 of the 28, 3-year old, heterozygous Watanabe heritable hyperlipidemic (WHHL-Hh) rabbits whose lipid profiles were presented in part I of this report. In situ perfusion fixation of the arteries showed 100% of the aortas involved with one or another type of intimal lesion. In male rabbits (n = 13), the abdominal aortas had more severe fibrosis and more diffuse intima thickening than the thoracic aortas, (p < 0.001). In female rabbits (n = 8), fatty streaks and fibrous lesions were more predominant in the thoracic than in the abdominal aorta (p < 0.05). Fatty aortic plaques in the female were more commonly found in the abdominal than in the thoracic aorta, but this finding was not statistically significant. In contrast, fatty aortic plaques were not found in the male aortas; however, larger areas of diffuse intimal thickening with fatty deposits were more common in the abdominal aortas of the males (p < 0.01). Annular arteriosclerotic lesions, exclusive to the thoracic aorta, occurred in three of 21 rabbits. Histologically, the aortas demonstrated subintimal fibrosis, fragmentation of the lamina elastica interna, focal medial degeneration, and cholesterol clefts. The coronary arteries were involved in 85% of the males and in 86% of the females. Lesions were more common in the left than in the right coronary artery and primarily consisted of mild nonobstructing intimal hyperplasia with fibrosis. Based on these observations, we consider older WHHL-Hh rabbits excellent models for studying atherosclerosis. Because of their genetic and age-related lesions, WHHL-Hh rabbits may be superior to the cholesterol-fed rabbit model with respect to comparability with human atherosclerotic lesions.