A model of primary atherosclerosis and post-angioplasty restenosis in mice.
Although mice deficient in various genes are providing greater insight into the mechanisms of restenosis after angioplasty, there have been limitations with murine models not simulating human vascular disease. To develop a more clinically applicable model of primary atherosclerosis and restenosis following angioplasty of the primary lesion, we fed apolipoprotein E-deficient mice a Western diet and occluded the left common carotid artery for 2 days. Three weeks after flow was restored, the temporarily occluded carotids demonstrated atherosclerotic lesions containing foam cells, cholesterol clefts, necrotic cores, and fibrous capsules. The atherosclerotic carotids in other animals underwent angioplasty with a beaded probe, resulting in plaque and medial layer disruption. Three weeks after angioplasty, although there was significant neointimal lesion formation, the luminal narrowing did not change significantly secondary to overall vessel enlargement (positive remodeling). Neointimal lesions were composed of smooth-muscle cells and extracellular matrix observed adjacent to the original atherosclerotic plaques. Similarly, even at 3 months after the angioplasty the lumen was maintained despite greater neointimal lesion formation caused by progressive positive remodeling. This new murine model of primary atherosclerosis and postangioplasty intimal hyperplasia and remodeling mimics the human disease pattern of postangioplasty intimal hyperplasia. Used in transgenic animals, this model will likely facilitate understanding of the mechanisms of restenosis in humans.
Leidenfrost
Jeremy E
JE
Department of Surgery, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Khan
M Faisal
MF
Boc
Kenneth P
KP
Villa
Brian R
BR
Collins
Emily T
ET
Parks
William C
WC
Abendschein
Dana R
DR
Choi
Eric T
ET
D017130:Angioplasty; D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics; D001161:Arteriosclerosis / Q000473:pathology / Q000601:surgery*; D002339:Carotid Arteries / Q000473:pathology* / Q000601:surgery; D016893:Carotid Stenosis; D002784:Cholesterol / Q000097:blood; D004032:Diet; D004195:Disease Models, Animal; D006801:Humans; D006965:Hyperplasia / Q000473:pathology; D008026:Ligation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012008:Recurrence
D001057:Apolipoproteins E; D002784:Cholesterol