Lipid retention in the arterial wall of two mouse strains with different atherosclerosis susceptibility.
LDL deposition in the subendothelium of arterial walls is the initial event in the development of atherosclerosis. The deposited LDL undergoes oxidative modification by arterial wall cells to become oxidized LDL and consequently contributes to atherosclerotic formation. Using mouse strains C57BL/6J (B6) and C3H/HeJ (C3H), which differ markedly in susceptibility to atherosclerosis, we determined whether variation in subendothelial retention of apolipoprotein B (apoB)-containing lipoproteins constitutes a genetic component in atherosclerosis. Lipoprotein retention was quantitated by Western blot analysis to detect the presence of apoB in aortic walls before foam cells developed. In both dietary and apoE-deficient models, B6 mice exhibited up to a 2-fold increase of apoB in the aortic wall compared with C3H mice. This increase could not be attributed to differences in plasma lipid levels of the two strains. In vitro, endothelial cells from C3H mice took up more acetylated and oxidized LDL but not native LDL and converted more native LDL to oxidized LDL than did endothelial cells from B6 mice. C3H mice expressed more scavenger receptor A in their aortic wall than B6 mice. Thus, variation in the subendothelial retention of apoB-containing lipoproteins cannot explain the dramatic difference in atherosclerosis susceptibility between B6 and C3H mice, and endothelial cells may play a role in alleviating lipid accumulation in arterial walls.
Brown
Morry D
MD
Department of Radiology, University of Virginia, Charlottesville, VA 22908, USA.
Jin
Li
L
Jien
Ming-Len
ML
Matsumoto
Alan H
AH
Helm
Gregory A
GA
Lusis
Aldons J
AJ
Frank
Joy S
JS
Shi
Weibin
W
D000107:Acetylation; D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000648:ultrastructure; D001055:Apolipoproteins B / Q000097:blood; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D001161:Arteriosclerosis / Q000097:blood* / Q000235:genetics / Q000473:pathology*; D008078:Cholesterol, LDL / Q000378:metabolism; D004198:Disease Susceptibility / Q000097:blood; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D005260:Female; D008055:Lipids / Q000097:blood*; D051379:Mice; D018345:Mice, Knockout; D008854:Microscopy, Electron; D010084:Oxidation-Reduction
D001055:Apolipoproteins B; D001057:Apolipoproteins E; D008078:Cholesterol, LDL; D008055:Lipids