Effects of Cholesterol Diets on Vascular Function and Atherogenesis in Rabbits

Abstract

Vascular endothelial dysfunction is an important early event in atherogenesis. To evaluate the effects of different levels of cholesterol-containing diets on vascular function and atherogenesis, 17 New Zealand White male rabbits were randomized into four groups: Control with noncholesterol, 10-week 0.5% (0.5C-10) or 1% cholesterol (1C-10), and 14-week 0.5% cholesterol (0.5C-14) feedings. After 10 or 14 weeks, the aortas were harvested for studies of vascular endothelial function and percentage surface lipid lesions. The 0.5% and 1% cholesterol feedings resulted in the same degree of hypercholesterolemia independent of the level and period of cholesterol feeding. There was a decreased trend in vascular endothelial-dependent relaxation to acetylcholine in cholesterol-fed rabbits. Fourteen-week cholesterol feeding induced the least vascular dilation at a concentration of 10-7 M acetylcholine (-38 +/- 3%, -23 +/- 4%, -23 +/- 2%, and -15 +/- 5% in control, 0.5C-10, 1C-10, and 0.5C-14 groups, respectively, P = 0.003). More cumulative exposure of arterial walls to cholesterol induced more surface lipid lesions in the aorta (r = 0.877, P < 0.001). There was a negative relationship between aortic lesions and vasodilation (r = -0.557, P = 0.020 for calcium ionophore; r = -0.463, P = 0.062 for acetylcholine). We conclude that the 0.5% and 1% cholesterol feedings induce similar degrees of hypercholesterolemia. However, aortic lipid lesions and vascular reactivity are dependent on cumulative exposure to cholesterol rather than serum cholesterol level only. Furthermore, decreased vascular endothelial relaxation in cholesterol-fed rabbits was related to lipid plaques in the aorta.

Expression of TNF-α and IL-6 cytokines in the choroid and sclera of hypercholesterolemic rabbits

“…In this study, the administered dosage of cholesterol was higher than that used in other studies (1% cholesterol), which enabled the authors to obtain immunohistochemical alterations of the choroid-sclera complex during a period of eight weeks. This demonstrated that alterations in the ocular walls as well as the arteries (32) could be brought about in a shorter period, thus offering opportunities for more experiments and reducing the costs. The NG group underwent euthanasia after 4 weeks.…”

“…The advantages of using rabbits over other animals include increased availability, low costs (when compared with transgenic mice lacking receptors for LDL cholesterol or apolipoprotein E), and a better genetic characterization (31) . Additionally, the hypercholesterolemic diet rapidly induces endothelial dysfunction and a response similar to atherogenesis, making it a good model for cardiovascular diseases (32) . Further, the normal serum cholesterol levels in rabbits range from 25 to 60 mg%, whereas in humans this variation is between 100 and 200 mg%.…”

“…Further, the normal serum cholesterol levels in rabbits range from 25 to 60 mg%, whereas in humans this variation is between 100 and 200 mg%. Therefore, the metabolic system of rabbits may readily be overloaded with a simple daily hypercholesterolemic diet, making the experiments more feasible and reproducible (32) . Indeed, the total serum cholesterol level in HG group increased from 41.3 mg/dL at the start of the experiment to approximately 2146.8 mg/dL at the time of euthanasia.…”

Rosiglitazona e lesão vascular em coelhos hipercolesterolêmicos: avaliação da formação neointimal

“…The animal model used here was based on previous studies in which rabbits rapidly develop hypercholesterolemia after excessive cholesterol feeding 15,16,22,23 .…”

Apolipoprotein A-I and lecithin:cholesterol acyltransferase transfer induce cholesterol unloading in complex atherosclerotic lesions

“…Feeding 0.15% cholesterol induced a pathophysiologically relevant degree of hypercholesterolemia and resulted in a decrease of HDL cholesterol. A decrease of HDL cholesterol following cholesterol feeding in rabbits has previously been observed [24][25][26][27] but the mechanism has not been investigated. Compared to short-term feeding of high amounts of cholesterol, 28 feeding low percentages of dietary cholesterol for longer durations has been reported to produce more advanced lesions as well as complicated lesions containing cholesterol clefts and necrotic debris.…”