Two Patterns of Lipid Deposition in the Cholesterol-Fed Rabbit

Abstract

Abstract-A central feature of arterial lipid deposition is its nonuniform and variable distribution. In immature human and rabbit aortas, spontaneous lesions occur most frequently downstream of branch points, but they tend to occur upstream of the same branches at later ages. In cholesterol-fed rabbits, the juvenile pattern has been seen regardless of age. These distributions may be determined by transport properties of the arterial wall, because uptake of plasma macromolecules is elevated downstream of aortic branches in immature rabbits and upstream in mature ones, except during cholesterol feeding, when the juvenile pattern is seen in adult vessels. The effect of cholesterol could reflect its inhibitory influence on the nitric oxide (NO) pathway because the adult transport pattern is NO dependent. Using protocols expected to preserve NO function and the mature pattern of transport during hypercholesterolemia, we made 2 attempts to induce upstream disease in rabbits. In trial I, plasma concentrations of cholesterol were kept within the normal human range for 15 weeks by using dietary levels of 0.05% to 0.2%. Although disease patterns reverse with age in human vessels exposed to these concentrations, lesions in both immature and mature rabbits occurred downstream of intercostal branch ostia. Trial II used older rabbits, a different base diet containing more vitamin E (96 mg/kg rather than 57 mg/kg), and higher levels of cholesterol (1%, administered for 8 weeks). For some animals, extra vitamin E (2000 mg/kg) was added to the diet. The mature pattern of lipid deposition was apparent around intercostal branches in the first group and was accentuated by the additional vitamin E, a change that was associated with a significant increase in the plasma concentration of NO metabolites. Spontaneous lesions, assessed on the base diet, were too rare to have influenced these distributions. This is the first report of upstream disease in the cholesterol-fed rabbit. The results support but do not prove the view that NO and transport are important in atherogenesis. (Arterioscler Thromb Vasc Biol.

α-Tocopherol protects against diet induced atherosclerosis in New Zealand white rabbits

“…Several studies of New Zealand white rabbits fed a cholesterol-rich diet supplemented with ␣-tocopherol have reported lower TPC concentrations compared with animals consuming low levels of dietary ␣-tocopherol (57-59, 61, 70, 71, 79), although two studies reported no change in TPC concentration (54,74). In the absence of added cholesterol, ␣-tocopherol does not lower TPC (1,(75)(76)(77). In this study, the non-HDL fraction, e.g., VLDL, IDL, and LDL, underwent the greatest reduction with dietary ␣-tocopherol supplementation as has been reported in other studies (57,58,72).…”

“…Two studies reported no change in TPC concentrations in both male and female New Zealand white rabbits (54,74). In the absence of added cholesterol, ␣ -tocopherol did not lower the TPC concentration (1,(75)(76)(77). ␣ -Tocopherol supplementation did not prevent lesion development in injured rabbit arteries but did reduce lipid peroxidation (78).…”

Effect of Reynolds number and flow division on patterns of haemodynamic wall shear stress near branch points in the descending thoracic aorta

“…Nuclear shape is approximately the same upstream and downstream of branches in both immature and mature mice (Bond & Weinberg 2006). Figure 9a-c shows the patterns of aortic lesion frequency around intercostal ostia in apolipoprotein E/ low-density lipoprotein receptor double knockout mice (McGillicuddy et al 2001), immature cholesterol-fed rabbits and mature cholesterol-fed rabbits (Barnes & Weinberg 1999), respectively. The comparatively uniform pattern of WSS n we found for the lowest values of Re and Q b : Q a (figure 2a) correlates with the approximate circumferential uniformity of lesion frequency seen in mice of all ages (figure 9a).…”

Distribution of Lipid Deposits Around Aortic Branches of Mice Lacking LDL Receptors and Apolipoprotein E

“…20 -22 In the present study, we examined whether the downstream distribution or a more upstream one, or a switch with age from the former to the latter, occurs in mice. We studied the origins of the intercostal arteries because these sites have been extensively studied a range of other species, because they are the only locations where age-related distributions paralleling those at human branches have been demonstrated in an animal model, 23,24 Eleven males aged 9 to 20 weeks were used in the present study. To confirm their broad similarity to the animals used in previous studies, total plasma cholesterol levels were determined in 2 mice by using a commercial enzymatic kit (Boehringer-Mannheim) and averaged 534 mg/dL.…”

“…20 -22 In the present study, we examined whether the downstream distribution or a more upstream one, or a switch with age from the former to the latter, occurs in mice. We studied the origins of the intercostal arteries because these sites have been extensively studied a range of other species, because they are the only locations where age-related distributions paralleling those at human branches have been demonstrated in an animal model, 23,24 and because there are large numbers in each aorta. We used apoE/LDLR double-knockout mice 25 because their disease develops sufficiently quickly that it can be mapped in young animals.…”