Abstract
The diet-induced atherosclerotic rabbit is an ideal model for atherosclerosis study, but temporal changes in atherosclerotic development in hypercholesterolemic rabbits are poorly understood. Japanese white rabbits were fed a high-cholesterol diet to induce sustained hypercholesterolemia, and each group of 10–12 animals was then sacrificed at 6, 12, 16, or 28 weeks. The rabbit aortas were harvested, and the sizes of the gross and intima atherosclerotic lesions were quantified. The cellular component of macrophages (Mφs) and smooth muscle cells (SMCs) in aortic intimal lesions was also quantified by immunohistochemical staining, and the correlation between plasma cholesterol levels and the progress of atherosclerotic lesions was studied. The ultrastructure of the atherosclerotic lesions was observed by transmission electron microscopy (TEM). Widely variable atherosclerotic plaques were found from 6 weeks to 28 weeks, and the lesional progress was closely correlated with cholesterol exposure. Interestingly, a relatively reduced accumulation of Mφ, an increased numbers of SMCs, and a damaged endothelial layer were presented in advanced lesions. Moreover, SMCs were closely correlated with cholesterol exposure and lesional progress for the whole period. Cholesterol exposure directly determines atherosclerotic progress in a rabbit model, and the changes in the cellular component of advanced lesions may affect plaque stability in an atherosclerotic rabbit model.
Highlights
Atherosclerosis is characterized by chronic inflammation in arteries that involves the accumulation of oxidized lipoproteins, an increased number of inflammatory cells and hypertrophic degeneration of the arterial intima, and it is closely associated with hypercholesterolemia [1,2,3]
The mechanism of plaque rupture is unclear, numerous studies have suggested that altered plaque contents result in destabilization, and these studies indicate that macrophages (Mφs) and smooth muscle cells (SMCs) in the lesion play pivotal roles in plaque rupture [5,6,7,8,9]
Hypercholesterolemia is strongly believed to contribute to atherosclerosis development in humans and in animal models, the temporal relationships between cholesterol exposure, atherosclerotic progression, and the changes in lesional cellular composition are not fully understood [3, 16, 17]
Summary
Atherosclerosis is characterized by chronic inflammation in arteries that involves the accumulation of oxidized lipoproteins, an increased number of inflammatory cells and hypertrophic degeneration of the arterial intima, and it is closely associated with hypercholesterolemia [1,2,3]. The temporal process of Mφs and SMCs accumulation in atherosclerotic lesions in rabbit is unclear, and the relationship between cholesterol exposure and the changes of cellular component is not completely determined. The pathological mechanism underlying Mφ death and defective resolution of inflammation remains uncertainly. To address these questions, we performed this study to investigate the temporal changes in development of atherosclerosis at four time points (6, 12, 16, and 28 weeks) in rabbits, as well as the potential relationship between the changes of cellular component and Journal of Biomedicine and Biotechnology Atherosclerotic lesion development
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