Characterization of diet induced aortic atherosclerosis in Syrian F1B hamsters

摘要

We characterized atherosclerotic lesions in Syrian F1B hamsters fed a diet high in saturated fat and cholesterol. Total cholesterol, non-high-density lipoprotein cholesterol, and triglycerides were significantly higher for treated animals than for low fat controls. After 4, 12, 18, 26, 32 and 44 weeks on either diet, the vasculature was fixed in situ and the aortic arch prepared for light and electron microscopy and immunohistochemistry. Fatty streak lesions comprised of foam cells were noted at 4 weeks along the inner curvature of the aortic arch. Fibromuscular lesions became evident at 26 weeks with excess connective tissue and a thickened media. Lesion size increased as foam cells accumulated in the subendothelial space and collagen was deposited in the upper media beneath an intact internal elastic lamina. By 44 weeks an advanced lesion had developed that consisted of a smooth muscle and extracellular matrix cap with an intact endothelium over a lipid rich core. The core consisted of foam cells, extracellular lipid, necrotic debris, cholesterol clefts, calcium deposits, and extracellular proteins. Oxidized LDL was only detected in the treated hamsters and localized to foam cells in early lesions, spread to extracellular matrix in fibrofatty lesions, and further involved medial smooth muscle cells in advanced lesions. Cyclooxygenases-1 and -2 were observed at low levels in both groups however, cyclooxygenase-2 was noticeably upregulated in the early lesions of treated animals. Atherosclerotic lesions similar to each major stage of pathology in humans developed at a predictable site in the hamster aorta in a relatively short period.