The effect of the duration of cholesterol feeding on the development of sudanophilic lesions in the rabbit aorta

Roach, Margot R.; Fletcher, Joan; Cornhill, J. Fredrick

doi:10.1016/0021-9150(76)90043-5

Cited by 42 publications

(12 citation statements)

References 4 publications

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“…The model of atherosclerosis used in the present study is well established and reproducible. 16,21,22 Rabbits fed a 1% cholesterol diet for 8 weeks developed fatty streaks involving Ϸ60% of the surface area of the aortic arch, which were characterized by infiltration by lipid-laden foam cells and VSMCs. The absence of increased circulating ET-1 is further evidence of the early nature of this model because circulating ET-1 concentration correlates with atherosclerosis disease burden.…”

Section: Discussionmentioning

confidence: 99%

Modulation of Functionally Active Endothelin-Converting Enzyme by Chronic Neutral Endopeptidase Inhibition in Experimental Atherosclerosis

Grantham¹,

Schirger²,

Wennberg³

et al. 2000

Circulation

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Background-Endothelin-converting enzyme-1 (ECE-1) processes big endothelin-1 (ET-1) to ET-1, a peptide implicated in atheroma formation. ECE-1 exists in 2 isoforms (ECE-1␣ and ECE-1␤), the result of alternative splicing of a common gene. Neutral endopeptidase (NEP) is a genetically distinct metallopeptidase that degrades the natriuretic peptides. These peptides mediate antiproliferative and vasodilating actions. We sought to demonstrate the distribution of the 2 ECE-1 isoforms in experimental atherosclerosis, to determine the effects of chronic NEP-I on plasma cGMP concentrations, vascular wall ECE-1 activity, and ET-1 concentration, and to correlate these actions with atheroma formation. Our hypothesis was that chronic NEP-I, in association with augmented cGMP, would inhibit ECE-1 conversion of big ET-1 to active ET-1, thus reducing tissue ET-1 concentrations and associated atheroma formation. Methods and Results-Cholesterol-fed New Zealand White rabbits (nϭ8, 1% cholesterol diet) and NEP-I-treated cholesterol-fed New Zealand White rabbits (nϭ8; candoxatril, 30 mg/kg per day, Pfizer) were euthanized after 8 weeks of feeding. ECE-1␣ and ECE-1␤ immunoreactivity was present in the aortas of both groups. Compared with control values, plasma cGMP concentrations were increased (2.8Ϯ0.6 versus 8.4Ϯ1.2 pmol/mL, PϽ0.05), ECE-1 activity was attenuated (68Ϯ3% versus 32Ϯ8%, PϽ0.05), aortic tissue ET-1 concentrations were reduced (4.6Ϯ0.5 versus 3.2Ϯ0.3 pg/mg protein, PϽ0.05), and atheroma formation was attenuated (62Ϯ6% versus 34Ϯ5%, PϽ0.01) by NEP-I. Conclusions-These studies suggest that ECE-1 is present and functionally active in the vascular wall in atherosclerosis.Inhibition of ECE-1 by NEP-I represents a novel approach to interruption of the endothelin system in this cardiovascular disease state.

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Section: Discussionmentioning

confidence: 99%

Modulation of Functionally Active Endothelin-Converting Enzyme by Chronic Neutral Endopeptidase Inhibition in Experimental Atherosclerosis

Grantham¹,

Schirger²,

Wennberg³

et al. 2000

Circulation

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“…Atherosclerosis can occur anywhere in arteries but is particularly prevalent on the inner wall of curved arteries and the outer wall of bifurcations. Cholesterol level [1][2][3][4][5], obesity, diet, smoking [6], drinking, diabetes [7] and 520 K. E. LEE ET AL.…”

Section: Introductionmentioning

confidence: 99%

“…Among various risk factors, the concentration of cholesterol in blood has been considered the most important factor since the plaques are rich in lipid [1][2][3], and this has been studied experimentally in various animals by feeding them with a diet containing cholesterol [4,5].…”

Section: Introductionmentioning

confidence: 99%

The spectral/hp element modelling of steady flow in non‐planar double bends

Lee

Parker

et al. 2007

Numerical Methods in Fluids

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SUMMARYThe purpose of this study is to better understand steady flow in three-dimensional non-planar double bend geometries which are chosen to loosely model a right coronary or femoral artery, neglecting branches. The knowledge gained from idealized geometries can subsequently be applied to anatomically correct geometries. The three-dimensional computations of steady flows in planar and non-planar double bends at Reynolds numbers of 125 and 500 were performed using a high accuracy, spectral/ hp element NavierStokes solver. In this study, we analyse the haemodynamics in terms of various mechanical factors (i.e. axial velocity, secondary flows, vorticity and coherent vortical structures). Although the effects of curvature and non-planarity on the flows are complex and often non-intuitive, from the numerical results, we can simplify and anticipate the secondary flow patterns, and by associations the wall shear stress distribution, in various double bend geometries with different non-planarities at physiological Reynolds number (100 Re 500). Non-planarity has the biggest effects on mixing and swirling of flow as observed through the coherent vortical structures and asymmetric secondary flow streamlines.

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“…14 The difference, however, is that the aortic arch of rabbits is highly susceptible to atherosclerosis, 11 whereas these proximal sites in the pigeon artery are relatively resistant to atherosclerosis (References 16-19; Figure 4). A possible explanation for this apparent discrepancy may be that there is a difference in the part of the arterial 125 I-TC content that reflects undegraded LDL and that represents products of arterial LDL degradation at the proximal sites compared with the susceptible site.…”

Section: Discussionmentioning

confidence: 99%

“…2 -tion, can only explain part of the risk of atherosclerosis in human beings. 8 In addition, in humans 9 ' 10 and experimental animals, 11 " 13 atherosclerosis develops preferentially at certain susceptible arterial sites, whereas other adjacent sites are resistant to atherosclerosis. These observations suggest that other yet-to-be-identified "risk factors" acting at the level of the arterial wall may determine the regional differences in susceptibility to atherosclerosis within an individual and may also be responsible for some of the unexplained variability in the extent of atherosclerosis among different individuals.…”

Section: I-tc-ldl Cholesterol Accumulation In Two Othermentioning

confidence: 99%

Accumulation of 125I-tyramine cellobiose-labeled low density lipoprotein is greater in the atherosclerosis-susceptible region of White Carneau pigeon aorta and further enhanced once atherosclerotic lesions develop.

Schwenke

Clair

1992

Arterioscler Thromb

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Previous studies have suggested that greater arterial concentrations of undegraded low density lipoprotein (LDL) and/or greater arterial rates of LDL degradation may play role(s) in determining regional differences in arterial susceptibility to atherosclerosis in rabbits (Schwenke and Carew, Arteriosclerosis 1989;9:895-918). The White Carneau (WC) pigeon is also useful for investigating potential mechanism(s) that might account for regional variation in arterial susceptibility to atherosclerosis because atherosclerosis develops predictably in the aorta at the level of the cellac bifurcation (atherosclerosis-susceptible celiac site). In this study we sought to determine whether the 123 I-tyramine cellobiose (

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The effect of the duration of cholesterol feeding on the development of sudanophilic lesions in the rabbit aorta

Cited by 42 publications

References 4 publications

Modulation of Functionally Active Endothelin-Converting Enzyme by Chronic Neutral Endopeptidase Inhibition in Experimental Atherosclerosis

Modulation of Functionally Active Endothelin-Converting Enzyme by Chronic Neutral Endopeptidase Inhibition in Experimental Atherosclerosis

The spectral/hp element modelling of steady flow in non‐planar double bends

Accumulation of 125I-tyramine cellobiose-labeled low density lipoprotein is greater in the atherosclerosis-susceptible region of White Carneau pigeon aorta and further enhanced once atherosclerotic lesions develop.

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