BACKGROUND Hyperlipidemia, hypertension, cigarette smoking and diabetes are some major risk factors for atherosclerosis and cardiovascular disease. Repeated endothelial injury and enhanced focal intimal influx of plasma lipoproteins are the pivotal mechanisms involved in atherogenesis. We previously demonstrated that the endothelial cell turnover and associated endothelial permeability were significantly increased in the aorta of spontaneously hypertensive rats, chronic oral nicotine-treated rats, and streptozotocin-diabetic rats. In the present investigation, we examined the effects of hyperlipidemia on arterial endothelial cell turnover and transendothelial macromolecular transport in cholesterol-fed rats. METHODS Sixteen male Sprague-Dawley rats were fed a diet containing 5% cholesterol for 6 weeks. A group of 14 agematched rats fed a regular diet and maintained over the same time period, were served as the controls. In en face preparations of the thoracic aorta, mitotic endothelial cells were identified by hematoxylin staining, IgG-containing dead endothelial cells were identified by an indirect immunoperoxidase method, and endothelial leakage to Evans blue-albumin complexes was quantified by fluorescence microscopy. RESULTS The results showed that plasma cholesterol and triglyceride levels were higher in cholesterol-fed rats. The hyperlipidemic rats, compared to control rats, had higher values for the frequency of endothelial cell death (1.08 +/- 0.28% vs 0.75 +/- 0.16%), the frequency of endothelial cell mitosis (0.015 +/- 0.005% vs 0.013 +/- 0.003%) and the number density of Evans blue-albumin leaky foci (6.19 +/- 0.64/mm2 vs 5.23 +/- 0.76/mm2) in the aorta. CONCLUSIONS Similar to the situations in hypertension, nicotine consumption and diabetes, the observed trend of increases in the frequency of endothelial cell turnover and endothelial permeability to large molecules in the aorta of cholesterol-fed rats suggested that these changes may contribute to accelerated atherogenesis in hyperlipidemia. However, since rat is not a favored animal model for studies of dietinduced hyperlipidemia and atherosclerosis, further investigations using other animal models such as rabbit, are needed to verify these observations.