Aortic atherosclerotic plaque injury in apolipoprotein E deficient mice

The acute platelet response and chronic smooth muscle cell (SMC) proliferat ion following aortic injury in apolipoprotein E-deficient mice was investig ated. The purpose of this study was to evaluate whether thrombus formation would occur following plaque injury, to determine the type of thrombus that developed, and to evaluate SMC proliferation. Aortic injury was performed by squeezing the aorta between forceps. The response to injury reflects the findings primarily associated with plaque disruption. An attempt was made to exclude the use of injured vascular segments that showed marked injury t o the media to minimize the effects that medial SMCs may have in thrombus f ormation. Acute and chronic experiments following injury were terminated at 30 min and at 2 weeks, respectively. Injury in normal and heterozygous mic e and nonplaque injury in apolipoprotein E-deficient mice were accompanied by endothelial denudation. In apolipoprotein E-deficient mice, plaque injur y, which released plaque contents, foam cells and fragments of foam cells, was followed by thrombus formation that contained degranulating platelets m ixed with fibrin. Large platelet-fibrin aggregates were in close contact wi th disrupted plaques and were mixed with foam cell debris. In addition, sma ll thrombi were in nonplaque areas following plaque disruptions. These thro mbi were not associated with injury to the media and most likely represent a heightened thrombogenicity associated with plaque disruption. At 2 weeks following injury, a thickened neointima was present in both wild type and m utant mice. Lipid filled cells were seen only in the media but not in the i ntima of apo E - / - vessels at 2 weeks. The results suggest that plaque in jury in homozygous apolipoprotein E-deficient mice promotes platelet-fibrin thrombus formation and that these thrombi are primarily associated with di srupted plaque contents. The results also suggest that the platelet respons e and SMC proliferation induced by aortic injury are not altered by hyperli pidemia caused by apolipoprotein E deficiency. (C) 1998 Elsevier Science Ir eland Ltd. All rights reserved.