Quantitative Investigation of Sudanophilic Lesions around the Aortic Ostia of Human Fetuses, Newborn and Children

Sinzinger, H; Silberbauer, K; Auerswald, W

doi:10.1159/000158233

Cited by 39 publications

(32 citation statements)

References 11 publications

(13 reference statements)

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“…The nonuniform distribution of lesions was thought to be a useful way of establishing mechanisms and a test of the relevance of the model to human disease; attention was drawn to the similar pattern occurring in young children. Parallels between the distributions in hyperlipidemic rabbits 10 -16 and children 1 were later confirmed by quantitative mapping techniques. However, it also emerged that disease has a different distribution in adult human arteries.…”

Section: Discussionmentioning

confidence: 74%

Two Patterns of Lipid Deposition in the Cholesterol-Fed Rabbit

Barnes¹,

Weinberg²

1999

ATVB

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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.

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Section: Discussionmentioning

confidence: 74%

Two Patterns of Lipid Deposition in the Cholesterol-Fed Rabbit

Barnes¹,

Weinberg²

1999

ATVB

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“…In human foetuses, neonates and infants, fatty streaks occur around the downstream margins of these branch ostia (Sinzinger et al 1980). At later ages, however, they occur at the lateral and then the upstream margins (Sloop et al 1998), while advanced disease tends to completely surround the ostium (Mitchell & Schwartz 1965).…”

Section: Introductionmentioning

confidence: 99%

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

Kazakidi

Sherwin

Weinberg

2008

J. R. Soc. Interface.

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Atherosclerotic lesions are non-uniformly distributed at arterial bends and branch sites, suggesting an important role for haemodynamic factors, particularly wall shear stress (WSS), in their development. The pattern of lesions at aortic branch sites depends on age and species. Using computational flow simulations in an idealized model of an intercostal artery emerging perpendicularly from the thoracic aorta, we studied the effects of Reynolds number and flow division under steady conditions. Patterns of flow and WSS were strikingly dependent on these haemodynamic parameters. With increasing Reynolds number, WSS, normalized by the fully developed aortic value, was lowered at the sides of the ostium and increased upstream and downstream of it. Increasing flow into the side branch exacerbated these patterns and gave rise to a reversing flow region downstream of the ostium. Incorporation of more realistic geometric features had only minor effects and patterns of mean WSS under pulsatile conditions were similar to the steady flow results. Aspects of the observed WSS patterns correlate with, and may explain, some but not all of the lesion patterns in human, rabbit and mouse aortas.

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“…12 ' 3 Much effort has focused on the effects of hemodynamic shear stress on endothelial cells, since these cells are thought to play a pivotal role in atherogenesis. 4 In vivo studies have shown that the shape and orientation of endothelial cells is determined primarily by the blood flow.…”

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confidence: 99%