A quantitative study of the development of sudanophilic lesions in the aorta of rabbits fed a low-cholesterol diet for up to six months

Contrasting Patterns of Spontaneous Aortic Disease in Young and Old Rabbits

“…Representation is the same as that described in the legend to Fig 1, except that there are 20ϫ30 squares covering a total area of 6.6ϫ9.9 mm 2 and that the more elongated ostia occupy a region with a radius approximately 1.5-2.5 squares from the central "ϫ" in weanlings and up to 4.5 squares in old rabbits. upstream 6 quadrants, possibly reflecting differences in feeding protocols. In old rabbits, the highest frequency of spontaneous lipid deposition occurred upstream of the ostium, as at celiac branches in adult human aortas.…”

“…[2][3][4][5] In rabbits fed a cholesterol-enhanced diet, however, there is no evidence for a reversal with age: the juvenile pattern of sudanophilia is observed even in animals maintained on the diet well into maturity. [6][7][8] These distributions may be related to variations in the net uptake of plasma macromolecules by the arterial wall. In immature rabbits, uptake of circulating albumin is greater downstream of aortic branches than upstream, 9 but the opposite pattern is seen after the age of sexual maturity.…”

Slowed Progression or Elimination of Atherosclerosis by Low-Frequency Electrical Impulses

“…Nonuniform distribution of lesions has been considered a useful way to establish the mechanisms of atherosclerosis and has been considered useful in testing the relevance of the model to human disease. Although attention was drawn to the similar pattern of hyperlipidemia distribution, especially in the young, 16‐23 it was later noted that the disease has a similar distribution in the aorta but a different distribution in arteries. For these reasons, we used a rabbit model of atherosclerosis to study the abdominal aorta.…”

Animal Models of Atherosclerosis

“…Requirement of genetically modified mice (e.g., apoE-deficient, LRLD-deficient) Plasma lipid profile markedly different to humans Differences in the morphology of the arterial wall due to the small size of murine vessels (e.g., reduced thickness of the medial layer, lack of vasa vasorum) Absence of plaque rupture and luminal thrombosis in most vessels Short-term feeding with diets containing high amounts of cholesterol (1-2%) mostly induces macrophage-rich fatty streaks, while long-term diets with lower amounts of cholesterol (0.2-0.75%) generate more complex lesions, with VSMC infiltration and cholesterol deposits. 20,[24][25][26][27]29 In addition, it has been shown that complex atherosclerotic lesions can be induced in NZW rabbits by intermittent cycles of fat feeding with periods of normal diet. 27,30 A widely used alternative method to accelerate the development of advanced lesions in rabbits combines a high-fat/high-cholesterol diet with angioplasty-induced aortic denudation of the aorta, generally from the aortic arch to the iliac arteries.…”

“…23 In addition, the development of advanced and complex atherosclerotic plaques containing a lipid core surrounded by VSMCs generally requires long periods of cholesterol feeding in NZW rabbits (from 6 months to several years). [24][25][26][27] However, longterm fat feeding of rabbits is discouraging, because it is frequently accompanied by noxious side effects and increased mortality owing to hepatic toxicity. Moreover, it induces a massive inflammatory response that does not resemble the chronic low-grade inflammatory response associated to human atherosclerosis.…”