Aortic atherosclerotic plaque injury in apolipoprotein E deficient mice.
The acute platelet response and chronic smooth muscle cell (SMC) proliferation following aortic injury in apolipoprotein E-deficient mice was investigated. 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 to the media to minimize the effects that medial SMCs may have in thrombus formation. Acute and chronic experiments following injury were terminated at 30 min and at 2 weeks, respectively. Injury in normal and heterozygous mice and nonplaque injury in apolipoprotein E-deficient mice were accompanied by endothelial denudation. In apolipoprotein E-deficient mice, plaque injury, which released plaque contents, foam cells and fragments of foam cells, was followed by thrombus formation that contained degranulating platelets mixed with fibrin. Large platelet-fibrin aggregates were in close contact with disrupted plaques and were mixed with foam cell debris. In addition, small thrombi were in nonplaque areas following plaque disruptions. These thrombi 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 mutant mice. Lipid filled cells were seen only in the media but not in the intima of apo E -/- vessels at 2 weeks. The results suggest that plaque injury in homozygous apolipoprotein E-deficient mice promotes platelet-fibrin thrombus formation and that these thrombi are primarily associated with disrupted plaque contents. The results also suggest that the platelet response and SMC proliferation induced by aortic injury are not altered by hyperlipidemia caused by apolipoprotein E deficiency.
Reddick
R L
RL
Department of Pathology, University of Texas Health Science San Antonio, USA.
Zhang
S H
SH
Maeda
N
N
D000818:Animals; D001012:Aorta, Abdominal / Q000293:injuries / Q000473:pathology; D001018:Aortic Diseases / Q000097:blood / Q000150:complications / Q000473:pathology*; D001057:Apolipoproteins E / Q000097:blood / Q000172:deficiency*; D001161:Arteriosclerosis / Q000097:blood / Q000150:complications / Q000473:pathology*; D001792:Blood Platelets / Q000378:metabolism / Q000473:pathology; D002455:Cell Division; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000473:pathology; D005260:Female; D005337:Fibrin / Q000378:metabolism; D005838:Genotype; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL / Q000235:genetics; D009131:Muscle, Smooth, Vascular / Q000473:pathology*; D013927:Thrombosis / Q000097:blood / Q000209:etiology / Q000473:pathology
D001057:Apolipoproteins E; D005337:Fibrin