Ultrastructure of early lipid accumulation in ApoE-deficient mice

Apolipoprotein (apo) E-deficient mice develop severe hypercholesterolemia a nd have lesions that progress from fatty streaks to fibrous plaques distrib uted in lesion-prone areas throughout the aorta. Lesions develop in apoE-de ficient mice on a regular chow diet and will occur faster on a diet higher in cholesterol. Examination of the aortas from these mice on a chow diet by high-resolution, freeze-etch electron microscopy demonstrated lipid retent ion in the intima by 3 weeks of age. Lipid was retained in the matrix as in dividual particles between 33 and 48 nm in diameter, aligned along the coll agen fibrils and in aggregates consisting of lipid particles with average d iameters of 33 and 68 nm. Larger particles seemed to have formed from fusio n of smaller particles. Lipid retention was more widespread in 5- and 9-wee k-old mice. Monocyte attachment to endothelial cells was observed by electr on microscopy at 5 weeks of age. The appearance of the intimal lipid was si milar to that previously described in rabbit models and suggests that lipid interaction with matrix filaments and subsequent aggregation of lipid part icles are critical first steps in the process of foam cell formation.