Neointimal formation in two apolipoprotein E-deficient mouse strains with different atherosclerosis susceptibility.
C57BL/6 (B6) and C3H/HeJ (C3H) are two commonly used mouse strains that differ markedly in atherosclerosis susceptibility. In this study, we determined plaque formation after removal of the endothelium in the two strains carrying the mutant apolipoprotein E gene (apoE(-/-)). At 10 weeks of age, male B6.apoE(-/-) and C3H.apoE(-/-) mice underwent endothelial denudation of the left common carotid artery. Two weeks after injury, B6.apoE(-/-) mice developed significantly larger neointimal lesions in the vessel than their C3H.apoE(-/-) counterparts, although they had comparable plasma cholesterol levels on a chow diet. Feeding of a Western diet aggravated lesion formation in both strains, but the increase was more dramatic in B6.apoE(-/-) mice than in C3H.apoE(-/-) mice. Immunohistochemical and histological analyses demonstrated the presence of macrophage foam cells in neointimal lesions. We then compared neointimal growth in F1 mice reconstituted with bone marrow from B6.apoE(-/-) and C3H.apoE(-/-) mice. No significant lesions were observed 2 weeks after endothelial denudation in the mice reconstituted with bone marrow from either donor. Thus, these data indicate that foam cell formation contributes to neointimal growth in the hyperlipidemic apoE(-/-) model and that neither endothelial cells nor blood cells alone explain the dramatic difference between B6 and C3H mice in plaque formation.
Department of Radiology, University of Virginia Health System, Charlottesville, VA 22908, USA. ws4v@virginia.edu
Weibin
W
Shi
Hong
H
Pei
Joshua J
JJ
Fischer
Jessica C
JC
James
John F
JF
Angle
Alan H
AH
Matsumoto
Gregory A
GA
Helm
Ian J
IJ
Sarembock
D000821:Animal Feed; D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics* / Q000502:physiology*; D001158:Arteries / Q000378:metabolism* / Q000473:pathology*; D001161:Arteriosclerosis / Q000235:genetics / Q000473:pathology; D015153:Blotting, Western; D016026:Bone Marrow Transplantation; D002784:Cholesterol / Q000097:blood / Q000378:metabolism; D004727:Endothelium / Q000378:metabolism; D005487:Foam Cells / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D007150:Immunohistochemistry; D050356:Lipid Metabolism; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D008822:Mice, Transgenic; D008855:Microscopy, Electron, Scanning; D009389:Neovascularization, Pathologic; D013997:Time Factors; D017539:Tunica Intima / Q000473:pathology*
D001057:Apolipoproteins E; D002784:Cholesterol