Objective -The distribution of atherosclerotic lesions changes with age in human and rabbit aortas. We investigated if this can be explained by changes in patterns of blood flow and wall shear stress. Methods -The luminal geometry of thoracic aortas from immature and mature rabbits was obtained by micro-CT of vascular corrosion casts. Blood flow was computed and average maps of wall shear stress were derived. Results -The branch anatomy of the aortic arch varied widely between animals. Wall shear was increased downstream and to a lesser extent upstream of intercostal branch ostia, and a stripe of high shear was located on the dorsal descending aortic wall. The stripe was associated with two vortices generated by aortic arch curvature; their persistence into the descending aorta depended on aortic taper and was more pronounced in mature geometries. These results were not sensitive to the modelling assumptions.Conclusions -Blood flow characteristics in the rabbit aorta were affected by the degree of taper, which tends to increase with age in the aortic arch and strengthens secondary flows into the descending aorta. Previouslyobserved lesion distributions correlated better with high than low shear, and age-related changes around branch ostia were not explained by the flow patterns.
Diet-induced atherosclerotic lesions in the descending thoracic segment of rabbit aorta were analysed ex vivo by micro-attenuated total reflection (ATR)-Fourier transform infrared (FTIR) spectroscopic imaging. The distribution and chemical character of lipid deposits within the arterial wall near intercostal branch ostia were assessed in histological sections from immature and mature rabbits fed cholesterol with or without L-arginine supplements. Previous studies have shown that both these properties change with age in cholesterol-fed rabbits, putatively owing to changes in the synthesis of nitric oxide (NO) from L-arginine. Immature animals developed lesions at the downstream margin of the branch ostium, whereas lipid deposition was observed at the lateral margins in mature animals. Dietary L-arginine supplements had beneficial effects in mature rabbit aorta, with overall disappearance of the plaques; on the other hand, they caused only a slight decrease of the lipid load in lesions at the downstream margin of the ostium in immature rabbits. ATR-FTIR imaging enabled differences in the lipid to protein density ratio of atherosclerotic lesions caused by age and diet to be visualized. Lipid deposits in immature rabbits showed higher relative absorbance values of their characteristic spectral bands compared with those in immature L-arginine-fed rabbits and mature rabbits. The multivariate methods of principal component analysis (PCA) and factor analysis (FA) were employed, and relevant chemical and structural information were obtained. Two distinct protein constituents of the intima-media layer at different locations of the wall were identified using the method of FA. This approach provides a valuable means of investigating the structure and chemistry of complex heterogeneous systems. It has potential for in vivo diagnosis of pathology.
NO has several putative atheroprotective properties but its precursor, L-arginine, and inhibitors of its synthesis have had inconsistent effects on the extent of experimental atherosclerosis in rabbits. The location and character of experimental atherosclerosis differ between immature and mature rabbits; both phenomena have been attributed to changes with age in the NO pathway. We investigated whether the influence of dietary L-arginine on experimental atherosclerosis is also age-related. The frequency of lesions was mapped in the descending thoracic and upper abdominal aorta of immature and mature rabbits fed 1 % cholesterol, with or without supplementary L-arginine, for 8 weeks. Consistent with earlier data, the distribution of lesions around the branch points changed with age in control rabbits. The mean frequency of lesions was essentially the same at both ages. L-Arginine supplements had no effect on the distribution of lesions at either age. They significantly reduced the mean frequency of lesions in mature animals but not in immature animals. Thus, the atheroprotective effect of dietary L-arginine in cholesterol-fed rabbits increases with age.
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